甘肃棘豆生物碱抗肝癌活性及其对荷瘤小鼠免疫功能影响的研究
|
摘要
肝症是我国常见癌症之一,每年死于肝癌的患者约11万人,占全世界肝癌死亡人数的45%。病因目前尚未完全明了,可能是环境因素、病毒感染、食源性污染、肝炎癌变及免疫功能下降等综合作用的结果。由于发病机理多种多样,防治很难一蹴而就。目前治疗肝癌大多采用化学合成药物,在治疗过程中易产生毒副作用和多药耐药性。天然药物以其毒副作用低和不产生耐药性而引起研究者的高度关注。因此,筛选天然来源的肝癌药物成为药理学领域的研究热点。
甘肃棘豆是棘豆属有毒植物品种之一,其分布面积广,营养价值高,但毒性也很强,严重威胁着草原畜牧业的发展。目前,棘豆属植物的防除和综合利用研究已取得了显著的成效。但其药用研究不深入也不系统,本试验以甘肃棘豆生物碱部位为研究对象,选择了较为常见的小鼠移植性肝癌H22和人原发性肝癌QGY-7703两种细胞株,分别进行体内外抗肿瘤作用及其机制方面的研究,获得以下结果:
(1)生物碱分别用阳离子交换树脂和碱性环境溶剂提取法得到,采用碘化铋钾、硅钨酸和磷钼酸试剂进行生物碱定性检测,结果显示,所提生物碱部位沉淀反应显强阳性;出碱率碱性环境溶剂提取法(1.75%)高于阳离子交换树脂提取法(1.56%)。
(2)研究甘肃棘豆生物碱对小鼠移植性H22肝癌的影响。结果表明,甘肃棘豆生物碱低、中、高剂量组(0.25、0.5、1.0 g/kg体重)均可抑制小鼠实体型与腹水型肝癌的生长,抑瘤率和生命延长率分别为38.6%、43.2%、53.8%和45.1%、55.1%、59.4%。表明甘肃棘豆生物碱具有抑制小鼠移植性肿瘤H22生长的作用。
(3)对实体瘤小鼠瘤块进行肉眼观察发现,甘肃棘豆生物碱各剂量组小鼠肿瘤易于剥离,体积较小,紧实,血管不丰富。用高剂量组瘤块制备肿瘤病理切片镜检发现,甘肃棘豆生物碱抑制了肿瘤细胞的生长,部分细胞呈现坏死表现如核固缩、碎裂和溶解。
(4)免疫组化SP染色结果表明,甘肃棘豆生物碱干预了增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和抑制肿瘤基因p53蛋白的表达,说明其抗肿瘤作用机理之一在于干预了肿瘤细胞的增殖能力和增殖周期。
(5)甘肃棘豆生物碱高剂量组实体瘤小鼠肝、肾眼观色泽质地均正常,无病理学改变。病理切片镜检发现肝、肾细胞排列紧凑,结构清楚。表明甘肃棘豆生物碱剂量达到1.0 g/kg体重时不会引起小鼠毒性反应。
(6)对实体瘤小鼠免疫器官胸腺和脾脏指数进行分析,并用放免法测定肿瘤坏死因子(tumor necrosis factor,TNF)和白细胞介素-2(interleukin-2,IL-2)的浓度。结果发现甘肃棘豆生物碱各剂量组均可提高小鼠胸腺指数和脾脏指数以及血清中TNF和IL-2的含量。表明甘肃棘豆生物碱抗肝癌作用与其改善免疫功能有关。
(7)细胞毒性试验表明甘肃棘豆生物碱作用48h可显著抑制体外培养的人肝癌QGY-7703细胞的生长,剂量-效应呈正相关,相关系数为0.9886,半数抑制浓度(50% inhibiting concentration,IC50)为18.53μg/mL。但其对人外周血单核细胞抑制作用较弱,表明甘肃棘豆生物碱对细胞具有选择性,能特异性杀死肿瘤细胞。集落形成试验表明甘肃棘豆生物碱能显著降低QGY-7703细胞的增殖能力,且呈剂量-效应正相关性,相关系数是0.9929,IC50值为19.85μg/mL。
(8)细胞形态学观察和DNA片段化分析证实甘肃棘豆生物碱诱导QGY-7703细胞发生了凋亡,细胞出现皱缩、变圆,核染色质固缩、碎裂、边集,形成凋亡小体和DNA梯形带等明显的凋亡特征。乳酸脱氢酶活力测定表明甘肃棘豆生物碱作用QGY-7703细胞48h内,细胞主要经历了凋亡性的死亡方式。流式细胞仪检测结果证实了甘肃棘豆生物碱可诱导QGY-7703细胞凋亡。
(9)黏附抑制试验结果显示:甘肃棘豆生物碱部位不同剂量的处理组中,以高剂量组(100μg/mL)对细胞与胶原的黏附抑制作用最强,各组与对照组相比,差异具有统计学意义(P<0.05,P<0.01)。Boyden小室体外QGY-7703细胞的侵袭、迁移试验发现,不同浓度的甘肃棘豆生物碱处理细胞后,对QGY-7703肿瘤细胞株的迁移和侵袭能力与对照组相比均有不同程度的降低,呈一定的剂量依赖性,其中,以100μg/mL组对肿瘤细胞的侵袭能力、迁移能力的抑制作用最强,侵袭抑制率为37.83%,迁移抑制率为33.97%,提示甘肃棘豆生物碱对肿瘤的抑制作用不仅表现在抑制肿瘤细胞的生长和诱导细胞调亡,还能影响肿瘤细胞与基质的相互作用,从而抑制肿瘤的浸润转移。
(10)Western免疫印迹实验发现甘肃棘豆生物碱下调了B细胞淋巴瘤-2(b-cell lymphoma gene 2,bcl-2)和PCNA的表达量,而凋亡活化基因bax与肿瘤抑制基因p53的表达量增高。说明甘肃棘豆生物碱诱导的凋亡与bcl-2家族、p53和PCNA基因调控有关。
本试验多角度较系统地研究了甘肃棘豆生物碱抗肝癌的作用,并从甘肃棘豆生物碱改善机体免疫功能、诱导肿瘤细胞凋亡和抑制肿瘤的浸润转移等多方面探讨了其抗肿瘤的作用机制,为开发甘肃棘豆为新型天然抗癌药物奠定了理论基础。
Liver cancer is one of common malignant tumors threatening people health and life. In China every year there are 110 thousand people died from it. The number about occupys 45% of entire world. It may be resulted from environment factor, virus infection, food pollution, pathological changes of liver inflammation and reduction of immune function, and so on. The prevention and cure are difficult because of various pathogenesis. The therapy of liver cancer mostly uses chemosynthesis drugs at present, but side effects and multidrug resistance of chemosynthesis drugs become frequent in treatment. Naturally occurring drugs have been paid close attention by researcher for their low side-effect and no-drug-resistance. So screening naturally occurring drugs of anti-liver cancer becomes the study hotspot of pharmacology field.
Oxytropis Kansuensis Bunge is one of toxic whin category plants, which distributes abroad, has high nutrient value and toxicity, and seriously threatens the local stockbreading and causes massive economic losing. Now, the research of whin category plants in prevention or killing off and utilization has made good progress, but its officinal research is not in-depth and not systemic.
In our study, we investigated anti-liver cancer activity and its action mechanism of alkaloid from Oxytropis Kansuensis by animal model of transplanted tumor H22 in vivo and QGY- 7703 cells in vitro. The results were as follows.
(1) The alkaloid from Oxytropis Kansuensis was extracted by cation resin and basic solvent two methods, which qualitative detect by bismuth potassium iodide, silicotungstic acid and phosphomolybdic acid. The results showed that it is strongly positive of alkaloid precipitation reaction and cation resin and basic solvent two methods compared extraction yield the latter is higher(1.75%)than the former(1.56%).
(2) The study on anti-liver cancer activity of alkaloid from Oxytropis Kansuensis showed that alkaloid (0.25, 0.5, 1.0 g/kg body weight) inhibited the growth of liver cancer H22 harboring mice. The tumor inhibition rate of solid tumor harboring mice and the life prolong rate of ascites tumor harboring mice were 38.6%,43.2%,53.8% and 45.1%,55.1%,59.4% separately. It indicated that alkaloid from Oxytropis kansuensis significantly inhibited the growth of liver cancer-transplanted of mice.
(3) The observation with eyes on solid tumors showed that tumors of alkaloid groups were stripped easily, tumor volume was small, tumors were compact, and blood vessels were not abundant. Tumor slice in high dose alkaloids group showed that growth of tumor cells was inhibited and some tumor cells appeared necrosis such as pycnosis, breaking to pieces and dissolving of nuclear.
(4) The research discussed the anti-tumor mechanism of alkaloid from Oxytropis kansuensis with immunohistochemistry method. The result showed that alkaloid of Oxytropis kansuensis had direct effect on H22 cell, this role was associated with the express of proliferating cell nuclear antigen(PCNA) and p53 protein.
(5) The color and texture of liver and kidney in high dose alkaloid group were normality and no pathology change observed with eyes. The slices of liver and kidney indicated that cells of liver and kidney disposed compactly and cells structure was distinct. The results suggested that alkaloid dose up to 1.0 g/kg was no signs of toxicity to tumor harboring mice.
(6) The immune organ assay and radioimmunoassay suggested that alkaloid significantly increased the index number of thymus and spleen and the concentration of tumor necrosis factor and interleukin-2 in serum of solid tumor harboring mice. It showed that anti-liver cancer activity of alkaloid from Oxytropis kansuensis was related with improvement of immune function.
(7) The growth of cells was inhibited when QGY- 7703 cells cultured in vitro were treated with alkaloid of Oxytropis kansuensis for 48 h. The dose and effect appeared positive correlation. 50% inhibiting concentration (IC50) was 18.53μg/ml. But the cytotoxicity of alkaloid to human peripheral blood mononuclear cells was low. It suggested that cytotoxicity of alkaloid had selectivity and it could kill tumor cells specifically. The experiment of colony formation indicated that alkaloid reduced proliferation activity of QGY- 7703 cells and IC50 was 19.85μg/ml. The relation between dose and effect was positive.
(8) The observation of cell morphology and DNA fragmentation analysis verified that alkaloid induced apoptosis of QGY- 7703 cells. The cells appeared apoptosis characteristic such as cells shrinkage and rounding, nucleus chromatin pyknosis, break and gather to nuclear membrane, and apoptotic bodies and DNA ladder-shaped band formation. LDH activity assay demonstrated that apoptosis pathway was mainly responsible for QGY- 7703 cells death treated with alkaloid in 48 h. Flow cytometry analysis confirmed that alkaloid could induce QGY- 7703 cell apoptosis.
(9) Compared with the control group the adhesion ability of the QGY-7703 cell line was decreased significantly (P<0.01, P<0.05) after treatment with the alkaloid from Oxytropis kansuensis, the 100μg/ml group on the adhesion inhibiting ability was the most obvious. The Boyden chamber test showed that compared with the control group both the invasion and the motility abilities of the QGY-7703 cell line were decreased significantly(P<0.01)after treatment with the different alkaloid does. The relation between dose and effect was positive. Among the 100μg/ml group on the invasion and the motility inhibiting abilities was the most obvious. The invasion inhibiting rate was 37.83% and the motility inhibiting rate was 33.97%. It make clear that the inhibiting tumor effect not only is the inhibiting effect to the tumor cell itself but also is due to the interrelation between tumor cell and the periplast, which has significant effect to tumor infiltration and migration.
(10) Western blot showed that alkaloid up-regulated the expression of bax and p53 protein and down-regulated the expression of b-cell lymphoma gene 2(bcl-2) and PCNA protein. The results above suggested that apoptosis induced by alkaloid of Oxytropis kansuensis was modulated by bcl-2 family, p53 and PCNA together.
The study investigated anti-liver cancer effect of alkaloid of Oxytropis kansuensis systematically and discussed the action mechanism from the point of view of organism immunologic function, apoptosis and tumor infiltration and migration. It provided rationale to develop Oxytropis kansuensis as naturally occurring drug of anti-tumor.
甘肃棘豆是棘豆属有毒植物品种之一,其分布面积广,营养价值高,但毒性也很强,严重威胁着草原畜牧业的发展。目前,棘豆属植物的防除和综合利用研究已取得了显著的成效。但其药用研究不深入也不系统,本试验以甘肃棘豆生物碱部位为研究对象,选择了较为常见的小鼠移植性肝癌H22和人原发性肝癌QGY-7703两种细胞株,分别进行体内外抗肿瘤作用及其机制方面的研究,获得以下结果:
(1)生物碱分别用阳离子交换树脂和碱性环境溶剂提取法得到,采用碘化铋钾、硅钨酸和磷钼酸试剂进行生物碱定性检测,结果显示,所提生物碱部位沉淀反应显强阳性;出碱率碱性环境溶剂提取法(1.75%)高于阳离子交换树脂提取法(1.56%)。
(2)研究甘肃棘豆生物碱对小鼠移植性H22肝癌的影响。结果表明,甘肃棘豆生物碱低、中、高剂量组(0.25、0.5、1.0 g/kg体重)均可抑制小鼠实体型与腹水型肝癌的生长,抑瘤率和生命延长率分别为38.6%、43.2%、53.8%和45.1%、55.1%、59.4%。表明甘肃棘豆生物碱具有抑制小鼠移植性肿瘤H22生长的作用。
(3)对实体瘤小鼠瘤块进行肉眼观察发现,甘肃棘豆生物碱各剂量组小鼠肿瘤易于剥离,体积较小,紧实,血管不丰富。用高剂量组瘤块制备肿瘤病理切片镜检发现,甘肃棘豆生物碱抑制了肿瘤细胞的生长,部分细胞呈现坏死表现如核固缩、碎裂和溶解。
(4)免疫组化SP染色结果表明,甘肃棘豆生物碱干预了增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和抑制肿瘤基因p53蛋白的表达,说明其抗肿瘤作用机理之一在于干预了肿瘤细胞的增殖能力和增殖周期。
(5)甘肃棘豆生物碱高剂量组实体瘤小鼠肝、肾眼观色泽质地均正常,无病理学改变。病理切片镜检发现肝、肾细胞排列紧凑,结构清楚。表明甘肃棘豆生物碱剂量达到1.0 g/kg体重时不会引起小鼠毒性反应。
(6)对实体瘤小鼠免疫器官胸腺和脾脏指数进行分析,并用放免法测定肿瘤坏死因子(tumor necrosis factor,TNF)和白细胞介素-2(interleukin-2,IL-2)的浓度。结果发现甘肃棘豆生物碱各剂量组均可提高小鼠胸腺指数和脾脏指数以及血清中TNF和IL-2的含量。表明甘肃棘豆生物碱抗肝癌作用与其改善免疫功能有关。
(7)细胞毒性试验表明甘肃棘豆生物碱作用48h可显著抑制体外培养的人肝癌QGY-7703细胞的生长,剂量-效应呈正相关,相关系数为0.9886,半数抑制浓度(50% inhibiting concentration,IC50)为18.53μg/mL。但其对人外周血单核细胞抑制作用较弱,表明甘肃棘豆生物碱对细胞具有选择性,能特异性杀死肿瘤细胞。集落形成试验表明甘肃棘豆生物碱能显著降低QGY-7703细胞的增殖能力,且呈剂量-效应正相关性,相关系数是0.9929,IC50值为19.85μg/mL。
(8)细胞形态学观察和DNA片段化分析证实甘肃棘豆生物碱诱导QGY-7703细胞发生了凋亡,细胞出现皱缩、变圆,核染色质固缩、碎裂、边集,形成凋亡小体和DNA梯形带等明显的凋亡特征。乳酸脱氢酶活力测定表明甘肃棘豆生物碱作用QGY-7703细胞48h内,细胞主要经历了凋亡性的死亡方式。流式细胞仪检测结果证实了甘肃棘豆生物碱可诱导QGY-7703细胞凋亡。
(9)黏附抑制试验结果显示:甘肃棘豆生物碱部位不同剂量的处理组中,以高剂量组(100μg/mL)对细胞与胶原的黏附抑制作用最强,各组与对照组相比,差异具有统计学意义(P<0.05,P<0.01)。Boyden小室体外QGY-7703细胞的侵袭、迁移试验发现,不同浓度的甘肃棘豆生物碱处理细胞后,对QGY-7703肿瘤细胞株的迁移和侵袭能力与对照组相比均有不同程度的降低,呈一定的剂量依赖性,其中,以100μg/mL组对肿瘤细胞的侵袭能力、迁移能力的抑制作用最强,侵袭抑制率为37.83%,迁移抑制率为33.97%,提示甘肃棘豆生物碱对肿瘤的抑制作用不仅表现在抑制肿瘤细胞的生长和诱导细胞调亡,还能影响肿瘤细胞与基质的相互作用,从而抑制肿瘤的浸润转移。
(10)Western免疫印迹实验发现甘肃棘豆生物碱下调了B细胞淋巴瘤-2(b-cell lymphoma gene 2,bcl-2)和PCNA的表达量,而凋亡活化基因bax与肿瘤抑制基因p53的表达量增高。说明甘肃棘豆生物碱诱导的凋亡与bcl-2家族、p53和PCNA基因调控有关。
本试验多角度较系统地研究了甘肃棘豆生物碱抗肝癌的作用,并从甘肃棘豆生物碱改善机体免疫功能、诱导肿瘤细胞凋亡和抑制肿瘤的浸润转移等多方面探讨了其抗肿瘤的作用机制,为开发甘肃棘豆为新型天然抗癌药物奠定了理论基础。
Liver cancer is one of common malignant tumors threatening people health and life. In China every year there are 110 thousand people died from it. The number about occupys 45% of entire world. It may be resulted from environment factor, virus infection, food pollution, pathological changes of liver inflammation and reduction of immune function, and so on. The prevention and cure are difficult because of various pathogenesis. The therapy of liver cancer mostly uses chemosynthesis drugs at present, but side effects and multidrug resistance of chemosynthesis drugs become frequent in treatment. Naturally occurring drugs have been paid close attention by researcher for their low side-effect and no-drug-resistance. So screening naturally occurring drugs of anti-liver cancer becomes the study hotspot of pharmacology field.
Oxytropis Kansuensis Bunge is one of toxic whin category plants, which distributes abroad, has high nutrient value and toxicity, and seriously threatens the local stockbreading and causes massive economic losing. Now, the research of whin category plants in prevention or killing off and utilization has made good progress, but its officinal research is not in-depth and not systemic.
In our study, we investigated anti-liver cancer activity and its action mechanism of alkaloid from Oxytropis Kansuensis by animal model of transplanted tumor H22 in vivo and QGY- 7703 cells in vitro. The results were as follows.
(1) The alkaloid from Oxytropis Kansuensis was extracted by cation resin and basic solvent two methods, which qualitative detect by bismuth potassium iodide, silicotungstic acid and phosphomolybdic acid. The results showed that it is strongly positive of alkaloid precipitation reaction and cation resin and basic solvent two methods compared extraction yield the latter is higher(1.75%)than the former(1.56%).
(2) The study on anti-liver cancer activity of alkaloid from Oxytropis Kansuensis showed that alkaloid (0.25, 0.5, 1.0 g/kg body weight) inhibited the growth of liver cancer H22 harboring mice. The tumor inhibition rate of solid tumor harboring mice and the life prolong rate of ascites tumor harboring mice were 38.6%,43.2%,53.8% and 45.1%,55.1%,59.4% separately. It indicated that alkaloid from Oxytropis kansuensis significantly inhibited the growth of liver cancer-transplanted of mice.
(3) The observation with eyes on solid tumors showed that tumors of alkaloid groups were stripped easily, tumor volume was small, tumors were compact, and blood vessels were not abundant. Tumor slice in high dose alkaloids group showed that growth of tumor cells was inhibited and some tumor cells appeared necrosis such as pycnosis, breaking to pieces and dissolving of nuclear.
(4) The research discussed the anti-tumor mechanism of alkaloid from Oxytropis kansuensis with immunohistochemistry method. The result showed that alkaloid of Oxytropis kansuensis had direct effect on H22 cell, this role was associated with the express of proliferating cell nuclear antigen(PCNA) and p53 protein.
(5) The color and texture of liver and kidney in high dose alkaloid group were normality and no pathology change observed with eyes. The slices of liver and kidney indicated that cells of liver and kidney disposed compactly and cells structure was distinct. The results suggested that alkaloid dose up to 1.0 g/kg was no signs of toxicity to tumor harboring mice.
(6) The immune organ assay and radioimmunoassay suggested that alkaloid significantly increased the index number of thymus and spleen and the concentration of tumor necrosis factor and interleukin-2 in serum of solid tumor harboring mice. It showed that anti-liver cancer activity of alkaloid from Oxytropis kansuensis was related with improvement of immune function.
(7) The growth of cells was inhibited when QGY- 7703 cells cultured in vitro were treated with alkaloid of Oxytropis kansuensis for 48 h. The dose and effect appeared positive correlation. 50% inhibiting concentration (IC50) was 18.53μg/ml. But the cytotoxicity of alkaloid to human peripheral blood mononuclear cells was low. It suggested that cytotoxicity of alkaloid had selectivity and it could kill tumor cells specifically. The experiment of colony formation indicated that alkaloid reduced proliferation activity of QGY- 7703 cells and IC50 was 19.85μg/ml. The relation between dose and effect was positive.
(8) The observation of cell morphology and DNA fragmentation analysis verified that alkaloid induced apoptosis of QGY- 7703 cells. The cells appeared apoptosis characteristic such as cells shrinkage and rounding, nucleus chromatin pyknosis, break and gather to nuclear membrane, and apoptotic bodies and DNA ladder-shaped band formation. LDH activity assay demonstrated that apoptosis pathway was mainly responsible for QGY- 7703 cells death treated with alkaloid in 48 h. Flow cytometry analysis confirmed that alkaloid could induce QGY- 7703 cell apoptosis.
(9) Compared with the control group the adhesion ability of the QGY-7703 cell line was decreased significantly (P<0.01, P<0.05) after treatment with the alkaloid from Oxytropis kansuensis, the 100μg/ml group on the adhesion inhibiting ability was the most obvious. The Boyden chamber test showed that compared with the control group both the invasion and the motility abilities of the QGY-7703 cell line were decreased significantly(P<0.01)after treatment with the different alkaloid does. The relation between dose and effect was positive. Among the 100μg/ml group on the invasion and the motility inhibiting abilities was the most obvious. The invasion inhibiting rate was 37.83% and the motility inhibiting rate was 33.97%. It make clear that the inhibiting tumor effect not only is the inhibiting effect to the tumor cell itself but also is due to the interrelation between tumor cell and the periplast, which has significant effect to tumor infiltration and migration.
(10) Western blot showed that alkaloid up-regulated the expression of bax and p53 protein and down-regulated the expression of b-cell lymphoma gene 2(bcl-2) and PCNA protein. The results above suggested that apoptosis induced by alkaloid of Oxytropis kansuensis was modulated by bcl-2 family, p53 and PCNA together.
The study investigated anti-liver cancer effect of alkaloid of Oxytropis kansuensis systematically and discussed the action mechanism from the point of view of organism immunologic function, apoptosis and tumor infiltration and migration. It provided rationale to develop Oxytropis kansuensis as naturally occurring drug of anti-tumor.
引文
阿翰林,党贵生,张生武,等.1994.刚查县哈尔盖乡甘肃棘豆调查与灭治.青海畜牧兽医杂志,2:5-7
白洁. 2005.苦马豆素制备的研究进展.邯郸学院学报,15(3):66-68
曹光荣,赵宝玉,王凯. 1998.英得尔种羊场采用轮牧法预防棘豆中毒试验初报.动物毒物学,1-2:38-40
曹世龙. 2001.肿瘤学新理论与新技术.人民军医出版社
陈德坤,雷莉辉,郭战军,等. 2003.甘肃棘豆生物碱对小鼠外周血免疫细胞活性及数量的影响.中国兽医科技,33(5):34-36
陈东鸿,贺平. 1998.柴胡及甘草酸对小鼠肝细胞凋亡的影响.第四军医大学学报,19(3):279-280
陈丽娟,盛瑞兰,汪承亚,等.1998.AO/EB荧光染色法测定阿糖胞苷诱导HL-60细胞凋亡.中华血液学杂志,19(1):41-42.
陈绍淑,赵宝玉,高睿,等.2004.苦马豆素的免疫原性及抗肿瘤研究进展.天然产物研究与开发,16(1):66-70
陈绍淑,赵宝玉,何生虎,等. 2004.小鼠小花棘豆生物碱中毒的病理学观察.中国兽医科技,34(12):77-79
陈智超,李秋柏,邵菁,等. 2006.小白菊内酯对多发性骨髓瘤细胞的生长抑制及其凋亡诱导作用.中华医学杂志,86(28):1993-1996
戴卉敏,杨鸣琦,李锡杰,等. 2009.豆类丝核菌培养液中苦马豆素分离提取.安徽农业科学,37(28):13440-13440
戴林. 1996.增殖细胞核抗原与胃癌.国外医学-消化系疾病分册,16(1):3-5
丁伯良,王建辰,薛登民,等. 1995.奶山羊甘肃棘豆中毒卵巢、胎盘的病理学研究.中国兽医学报, 15(1):27-32
丁伯良,王建辰. 1994.甘肃棘豆对山羊精子形态和超微结构的影响.西北农业大学学报,22(2):44-49
丁志山,高承贤,陈铌铍,等. 2003.姜黄素具有抑制血管生成与诱导肿瘤细胞凋亡双重作用.中国药理学通报,19(2):171-173
方乐堃，潘凌霄，黎雅婷，等.2007.复方小柴胡汤对荷EAC鼠IL-2水平和CD4+/CD8+比值的影响.中国病理生理杂志,23(9):1720-1723
高冬,高永琳,白平. 2003.半枝莲对宫颈癌细胞钙信号系统的影响.中药材,26(10):730-733
葛金文,陈大舜. 1997.细胞凋亡在中医药研究中的地位.湖南中医学院学学报[J],17(3):68-70
苟晨,刘文明,童德文.2008. 3种苦马豆素人工抗原的合成及其免疫原性研究.西北农业学报,17(3):28-32
顾百群,曹光荣,薛登民. 1991.山羊甘肃棘豆中毒治疗初探.畜牧兽医杂志,2:11-14
郭小琴. 1997.口服补液盐对绒山羊棘豆草中毒的疗效.中国兽医科技,27(12):44
黄秀梅,李波. 2003.氧化苦参碱对TNFα、IL26和IL28的影响.中成药,25(11):903-906
黄益玲,黄利鸣,石新兰,等. 2005.天花粉蛋白对人宫颈癌HeLa细胞增殖和细胞调亡的影响.中国药理学通报,21(2):253-254
霍星华,赵宝玉,王建军,等. 2008.镰形棘豆化学成分预试及生物碱成分薄层色谱分析.西北农业学报,17(2):24-28,32
金伯泉. 2001.细胞和分子免疫学.北京:科学出版社,695-704
孔庆志,黄冬生,黄涛,等. 2003.三种中药注射剂对小鼠移植性S180肉瘤血管形成的抑制作用.中国医院药学杂志,23(11):646-648
孔庆志,黄涛,黄冬生,等. 2003.苦参素对小鼠移植性S180肉瘤血管形成的抑制作用.中国药师, 6(12):769-771
李建科,刘诩中,卢建雄,等. 1995.甘肃棘豆饲喂小白鼠的亚慢性毒性效应及安全利用研究.中国兽医科技,25(8):28-30
李建科,杨具田,卢建雄,等. 1997.甘肃棘豆草粉对肥育猪的效果和毒性试验.中国兽医科技,27(5):30-31
李建科. 1997.中国棘豆属植物开发利用研究现状及前景评述.草与畜杂志,4:3-5
李立,赵俊,刘文明,等. 2008.苦马豆素-HSA对小鼠免疫原性研究.西北农林科技大学学报(自然科学版),36(1):23-27
李嫔,田国才,林娜,等. 1998.广枣总黄酮对小鼠胸腺细胞凋亡及腺苷脱氧酶(ADA)活性的影响.中华微生物和免疫学杂志,18(6):386-391
李勤凡,王建华,刘志斌,等. 2005.萃取法提取甘肃棘豆中的苦马豆素研究初报.中国农学通报,21(5):143-145
李晓光,谢锦玉,李文梅. 1998.大蒜油诱导人胃癌细胞分化和凋亡的机制研究.中华肿瘤杂志,20(5):325-327
李锡杰,杨鸣琦,张伟,等. 2009.金龟子绿僵菌中苦马豆素的提取.精细化工,6:554-557
梁冰,颜世芬,陈茂齐,等. 1994.甘肃棘豆挥发性成分研究Ⅰ.精油成分分离与鉴定.分析测试学报, 13(1):37-43
梁克明,谢艳华,石梅,等. 2002.九节龙皂甙对Hela细胞生长的抑制作用.第三军医大学学报,24(6):725-728.
刘炳亚,林言箴. 1998.苦马豆素抑制胃癌生长及转移的试验研究.中华肿瘤杂志, 20(3):168-170
刘复生,刘彤华.1997.肿瘤病理学.北京:北京医科大学-中国协和医科大学联合出版社
刘铭,王明娟,刘伟,等. 2008.甘肃棘豆体内生物碱部位活性的研究.中国现代医药杂志,10(12):8-11
刘秋燕,吕占军,何小波,等. 2004.雷公藤内酯醇对人宫颈癌细胞的凋亡诱导效应.中国肿瘤生物治疗杂志,1l(1):36-38
刘巍,张晓彬,李雅,等.2006.苦马豆素的抑瘤和免疫增强作用.西北药学杂志,21(6):258-260
刘伟,张毓,王溪,等. 2008.植物生长季节不同栖息地高原鼠兔的食物选择.兽类学报,28(4):358-366
刘志滨,赵兴华,余永涛,等. 2006.甘肃棘豆中苦马豆素提取工艺改进初报.西北农林科技大学学报(自然科学版),34(1):97-99,104
路浩,王建军,孙莉莎,等. 2009.苦马豆素抗肿瘤作用研究进展.动物医学进展,30(9):87-90
卢萍,赵萌莉,韩国栋,等. 2006.内蒙古疯草及其研究进展.中国草地学报,28(1):63-68
马寿福,刁治民,张静,等. 2007.棘豆属毒草防治及开发利用.青海草业,16(2):33-37
马晓华,沃兴德,梁海曼. 1999.姜黄素抗肿瘤作用与诱导肿瘤细胞凋亡的研究概况.国外医学-肿瘤学分册,26(1):21-23
孟协中,张如明. 1995.甘肃棘豆中有毒生物碱的研究.草业学报,4(1):6-8
潘子民,叶大风,谢幸,等. 2002.人参皂甙Rg3对荷卵巢癌的严重联合免疫缺陷鼠的抗肿瘤血管生成作用的研究.中华妇产科杂志,37(4):227-230
彭黎明. 1999.吞噬细胞对凋亡细胞的识别与吞噬.中华护理学杂志,28:304-306
钱红兰,胡倩,胡旭东,等.2007.槐耳浸膏对骨髓瘤细胞增殖和凋亡的影响.中国热带医学,7(6):889-890
芮菊生,杜懋琴,陈海明,等. 1980.组织切片技术.上海:人民教育出版社
沈明华,莫重辉,赵宝玉,等.2010.家兔实验性甘肃棘豆中毒的临床症状和病理形态学观察.动物医学进展,31(1):44-49
施新猷. 1989.医用试验动物学.西安:陕西科学技术出版社
史志诚. 1996.中国草地重要有毒植物.北京:中国农业出版社
衰静,肖余. 1996.槲皮素抗肿瘤作用研究进展.国外医学-中医中药分册,18(4):3-5
税媛媛,刘文明,赵献军,等. 2007.4种偶联率的苦马豆素-HSA合成及其对小鼠免疫原性研究.西北农业学报,16(6):1-7
宋晓凯. 2004.天然药物化学.北京:化学工业出版社
苏长青,龚西渝.1996.细胞凋亡的形态特点及生物学意义.临床与试验病理学杂志,12(4):346-348
田菲,贾英杰,陈军,等. 2003.肺一丸对肺癌血管生成及转移影响的试验研究.天津中医药,20(5):56-58
童德文,曹光荣,耿果霞,等. 2003.薄层扫描测定5种疯草中苦马豆素含量.中国兽医学报,23(2):183-184
童德文,曹光荣,李绍君. 2001.甘肃棘豆中苦马豆素的分离与鉴定.西北农林科技大学学报(自然科学版),29(3):5-7
童德文,曹光荣,赵献军. 2001.HPLC分离甘肃棘豆中苦马豆素.西北农业学报,10(2):6-8
童德文,董强,刘文明,等. 2006.苦马豆素-BSA接种山羊的免疫学研究.中国兽医杂志,42(7):15-17
童德文,董强,赵宝玉,等. 2006.用甘肃棘豆草粉饲喂苦马豆素-BSA免疫山羊的血清相关酶分析.中国兽医科学,36(4):331-335
童德文,董强,赵宝玉,等. 2006.苦马豆素-BSA免疫山羊的血清相关酶评价.中国农业科学,39(11):2384-2389
童德文,赵宝玉,廉士刚,等. 2004.甘肃棘豆化学成分研究Ⅰ.碱水氯仿提取部位成分分析.中兽医医药杂志,23(5):13-16
王汉斌,庞琦,富壮,等.2010.雄黄体外诱导C6胶质瘤细胞凋亡的特点及分析.山东大学学报(医学版),1:21-24,29
王建军,赵宝玉,万学攀,等. 2008.苦马豆素的分离及其体外抗肿瘤作用.中国兽医杂志,44(2):70-71
王凯,莫重辉,赵宝玉,等. 1999.“棘防E号”预防绵羊甘肃棘豆中毒.畜牧与兽医,31(3):31-32
王凯. 1998.“棘防A号”试验性预防山羊甘肃棘豆中毒.中国兽医科技,28 (8):31-32
王明娟,刘铭,刘伟,等. 2009.甘肃棘豆生物碱部位体内抗肿瘤作用及对免疫功能的影响.中国中西医结合杂志,29(11):1009-1011
王银朝,赵宝玉,樊月圆,等. 2005.甘肃棘豆中苦马豆素的分离与鉴定.动物医学进展,1:8-10
沃兴德,丁志山,尹丽慧,等. 2003.参麦对小鼠移植瘤组织中bFGF和MMP-2表达的影响.肿瘤防治杂志,10(4):345-347
吴达,龙玲,张彦明. 2007.甘肃棘豆抗肿瘤活性成分的筛选.中国兽医科学,37(5):440-443
吴旭锦,杨鸣琦,白春黎,等.2005.苦马豆素的来源及分离方法进展.动物医学进展,26(5):41-44
伍银桥,王孟薇,吴本俨,等. 2003.胃癌前病变演变过程中凋亡相关蛋白和PCNA的表达意义.世界华人消化杂志,11(8):1219-1222
吴振,吴立军,田代真一,等. 2004.紫草素诱导HeLa细胞凋亡经过caspase激活的机制.中国药理学通报,20(5):540-544
夏凤琴,李延钩. 1996.细胞凋亡.国外医学-老年病学分册,17(3):123-125
肖东,顾振纶. 1998.槲皮素下调人白血病HL60细胞bcl-2基因表达.中国药理学报, 19(6):551-553
徐超,刘斌,石任兵.2008.棘豆属植物化学成分与药理作用.国外医药(植物药分册),23(1):1-7
徐叔云,卞如濂,陈修. 1991.药理试验方法学(第二版).北京:人民卫生出版社
徐中平,李福川,王海仁. 1999.昆布多糖硫酸酯的抑制血管生成和抗肿瘤作用.中草药,30(7):551-553
薛妍,夏天,赵建斌,等. 2000.姜黄素对人肝癌细胞SMMC-7721的抑制作用.第四军医大学学报,25(5):84-86
杨鸣琦,曹光荣,李绍君. 1998.苦马豆素对小白鼠移植性肿瘤S180、ARS的抑制试验.动物医学进展,19(2):26-29
叶思杰,刘建利,黄伟平.2009.抗癌天然产物苦马豆素的合成研究进展.有机化学,29(5):689-695
于珊,秦宝福. 2006.苦马豆素国内外研究进展.中国农村小康科技,6:63-67
余谦,李庆明,吴伟康,等. 2000.中药胃康宁对试验性胃癌PCNA、P53蛋白表达的干预作用.中山医科大学学报,21(10):1-7
余永涛,耿果霞,刘志滨,等. 2006.家畜毛瓣棘豆中毒研究.草业科学,23(5):75-77
曾文军,王柳均. 2005.细胞凋亡的流式细胞仪检测技术研究进展.Anthology of Medicine,24(3):425-428
张芳芳,杨光明,王栋,等.2010.镰形棘豆提取物抗肿瘤活性的体外实验研究.药学与临床研究,18(2):135-138
张生民,高其东,侯德慧,等. 1981.甘肃棘豆中毒.畜牧兽医学报,12(3):145-149
张守信,曹光荣,李绍君,等. 1992.甘肃棘豆醇提物对小鼠移植性肿瘤S37 H22的抑制试验.畜牧兽医杂志,2:13-15
张为民,蒲鹏,张德刚,等. 2005.从苦豆子种子中提取生物碱的方法研究.中国农学通报,21(2):7-9
张莹,张起辉,吴立军,等.2004.吴茱萸碱诱导人宫敬癌Hela细胞凋亡过程中非caspase调控因素.中国药理学通报,20(1):61-64
张志敏,王建华,赵兴华,等.2008.苦马豆素对小鼠腹腔巨噬细胞免疫功能的影响.中国农业科学,41(10):3422-3428
赵宝玉,曹光荣,童德文,等.“棘防C”预防山羊甘肃棘豆中毒初探.动物医学进展,1999,20(1):42-44
赵宝玉,王凯,曹光荣,等. 2001.甘肃棘豆毒性生物碱研究.中国兽医学报,21(2):173-176
赵宝玉,陈绍淑,莫重辉,等.2005.苦马豆素的提取分离及其抗肿瘤活性研究.毒理学杂志, 19(A03):252
赵敬,赵涌.2004.姜黄素对人宫颈癌细胞株Hela细胞抑制及凋亡的影响.重庆医科大学学报,29(3):296-299.
赵俊,童德文,税媛媛,等. 2006.甘肃棘豆草中苦马豆素的提取分离工艺比较研究.西北植物学报,26(7):1459-1463
周建军,乐秀芳,韩家娴,等. 1994.影响MTT方法测定结果的一些因素.肿瘤,14(2):93.
Adams JM, Cory S. 1999.The Bcl-2 Protein falllily: Arbiters of cell survival .Science, 281:1322-6.
Afshrihari C, Beuno M, Lamb P, et al. 2000.Interaction of the metastasis suppressing Proteins KAI l and E-cadherin in epithelial cells. Proc Am Assoc Cancer Res,40:197
Ajish Kumar KS, Chaudhari VD, Dhavale.2008. Efficient synthesis of (+)-1,8, 8a-tri- epi-swainsonine, (+)-1,2-di-epi-lentiginosine,(+)-9a-epi-homocastanospermine and (-)-9-deoxy-9a-epi- homocastanosper -mine from a D-glucose-derived aziridine carboxylate, and study of their glycosidase inhibitory activities. Org Biomol Chem, 6:703-711
Arakaki N, Kazi JA, Kazihara T, et al. 1998.Hepatocyte growth factor/scatter factor activates the apoptosis signaling pathway by increasing caspase-3 activity Sarcoma 180 cells. Biochemical and Biophysical Research Communication, 245:211-215
Ashley AK,Custis M, Ashley R, et al. 2006. Toxicokinetic profile of swainsonine following exposure to locoweed (Oxytropis sericea) in naive and previously exposed sheep. N Z Vet J, 54:34-40
Au CW, Pyne SG. 2006. Asymmetric synthesis of anti-1,2-amino alcohols via the Borono-Mannich reaction: a formal synthesis of (-)-swainsonine. J Org Chem, 71:7097-7099
Bates RW, Dewey MR. 2009. A formal synthesis of swainsonine by gold-catalyzed allene cyclization. Org Lett, 11:3706-3708
Bi J,Aggarwal VK. 2008.Application of furyl-stabilized sulfur ylides to a concise synthesis of 8a-epi- swainsonine. Chem Commun (Camb), 120-122
Call JA, Eckhardt SG, Camidge DR. 2008. Targeted manipulation of apoptosis in cancer treatment. Lancet Oncol ,9 :1002-1011
Caroline D, Scatena S. 1998. Mitotic phosphorylation of bcl-2 during normal cell cycle progression and taxol-induced growth arrest. Journal of Biological Chemistry, 273(46):30777-30781
Ceccon J, Greene AE, Poisson JF. 2006. Asymmetric [2 + 2] cycloaddition: total synthesis of (-)- swainsonine and (+)-6-epicastanospermine. Org Lett, 8:4739-4742
Chipuk JE, Kuwana T, Bouchier-Hayes L, et al. 2004.Direct activation of bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science, 303:1010-1014
Chooprayoon S, Kuhakarn C, Tuchinda P, et al. 2010.Asymmetric total synthesis of (+)-swainsonine. Org Biomol Chem
Christine D, Pozniak CD, Radinovic S, et al. 2000.An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science, 289(14):304-306
Colegate SM, Dorling PR, Huxtable CR. 1979.A spectroscopic investigation of swainsonine: an a mannosidase inhibitor isolated from Swainsina canecens. Aust. J. Chem,32:2257-2264
D. Mumberg PA, Monach S,Wanderling M, et al. 1999. CD4+ T Cells Eliminate MHC Class II-negative Cancer Cells in Vivo by Indirect Effects of IFN-γ. Immunology, 96:8633-8638
Dantas AF, Riet-Correa F, Gardner DR, et al. 2007. Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of Turbina cordata in Northeastern Brazil. Toxicon,49:111-116
Fei XF, Wang BX, Li TJ, et al. 2003.Evodiamine, a constituent of Evodiae fructs, induces anti-proliferating effects in tumor cells. Cancer Science, 94:92-98
Gao XH, Xu YX, Janakiraman N, et al. 2002. Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production. Biochemical Pharmacology, 62:1299-1308
Goss PE, Baptiste J, Fernandes B, et al. 1994. A phase I study of swainsonine in patients with advanced malignancies. Cancer Res, 54:1450-1457
Goss PE, Reid CL, Bailey D, et al. 1997. Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. Clin Cancer Res, 3:1077-1086
Grooss A, McDonnell JM, Korsmeyer SJ. 1999.Bcl-2 family members and the mitochondria in apoptosis. Genes Development, 13:1899-1911
Guo H, O'Doherty GA. 2006. De novo asymmetric synthesis of D- and L-swainsonine. Org Lett, 8:1609-1612
Guo H, O'Doherty, GA. 2008. De Novo Asymmetric Syntheses of d-, l- and 8-epi-Swainsonine. Tetrahedron , 64:304-313
Hafez SA, Caceci T, Freeman, et al. 2007.Angiogenesis in the caprine caruncles in non-pregnant and pregnant normal and swainsonine-treated does. Anat Rec (Hoboken), 290:761-769
Han SC,Yee K,Taeseok B, et al. 2006. Enhancement of Antitumor Immunity of Dendritic Cells Pulsed with Heat-treated Tumor Lysate in Murine Pancreatic Cancer. Immunol Lett, 103:142-148
Harris MH,Thompson CB. 2000.The role of the Bcl-2 family in the regulation of outer Mitochondrial membrane permeability.Cell Death Differ, 7:1182-91.
Hendrikse AS, Hunter AJ, Keraan M, et al. 2000. Effects of low dose irradiation on TK6 and U937 cell: induction of p53 and its role in cell-cycle delay and the adaptive response. International Journal of Radiation Biology, 76(1):11
Hengartner MO. 2000.The biochemistry of apoptosis.Nature, 407:770-6
Hueza IM, Guerra JL, Haraguchi, et al.2007. Assessment of the perinatal effects of maternal ingestion of Ipomoea carnea in rats. Exp Toxicol Pathol, 58:439-446
James LF, Panter KE.1991.Swainsonine-induced high mountain disease in calves. Vet. Hum. Toxicol, 33(3):217-219
Jens BH, Seiichi N, Ray M, et al. 2000. Oral administration of an estrogen metabolite-induced potentiation of radiation antitumor effects in presence of wild-type p53 in non-small-cell lung cancer. International Journal of Radiation Oncology Biology Physics, 48:1127-1137
Joza N,Susin SA,Daugas E,et al. 2001. Essential role of the mitochondrial apoptosis-inducing factor in Programmed cell death.Nature,410:549-54
Kerr JFR, Wyllie AH, Currie AR. 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer, 26:239
Korbakis D, Scorilas A. 2009. Treatment of gastric cancer cells with 5-fluorouracil/leucovorin and irinotecan induces distinct alterations in the mRNA expression of the apoptosis-related genes, including the novel gene BCL2L12. Tumour Biol , 30:100-107
Kuo ML.1996.Curcumin, an antioxidant and antitumor promoter, induces apoptosis in human leukemia cells. Biochemical Biophysical Acta, 1317(2):95-99
Li S, Chien S, Branemark PI. 1999. Heat shock-induced necrosis and apoptosis in osteoblasts. Journal of Orthopaedic Research, 17:891-899
Lin XD, Han C. 2000. Gap junctional communication and the tyrosine phosphorylation of connexin 43 in interaction between breast cancer and endothelial cells. World Journal of Gastroenterology, 6(5):699-703
Litynska A, Przybylo M, Pochec E, et al.2006. Does glycosylation of melanoma cells influence their interactions with fibronectin? Biochimie, 88:527-534
Maiden GH. 1901.Plants reputed to the poisnous to livestock in Australia. Dept. Agric, NSW, Misc. Publi, 10447
Majno G, Joris I. 1995.Apoptosis,oncosis,and necrosis,an overview of cell death.Am J Pathol, 146(l):3-15
Marsh CD. 1909.The locoweed disease of the plains. U.S. Department of Agriculture, Bureau of Animal Industry, Washington, D.C,1-130
Molyneux RJ, James LF, Panter KE. 1984. Chemistry of toxic consriruents of locoweed (Astragalus and Osytropis) species. Symposium, Plant Toxicology, Queensland, Austalia,The ueensland Poisnous Plants Committee, 266-278
Nagata S. 2000.Apoptotic DNA fragmentation. Exp.Cell Res, 10:12-18
Nakazawa Y, Kamijo T, Koike K, et al. 2003.ARF tumor suppressor induces mitochondria-dependent apoptosis by modulation of mitochondrial bcl-2 family proteins. Journal of Biological Chemistry, 278(30):27888-27895
Opez V, Charyulu B. 2002.Influence of Breast Cancer on Thymus Function in Mice. J Mammary Gland Biol Neoplasia, 7:191-199
Pataer A, Fanale MA, Roth JA, et al.2006. Induction of apoptosis in human lung cancer cells following treatment with amifostine and an adenoviral vector containing wild-type p53. Cancer Gene Ther 13, 806-814
Perl AK, Petra W, Ulf D. 1998.Acausal role for E-cadherin in the transition from adenoma to carcinoma. Nture, 392(l):190-193
Pochec E, Litynska A, Bubka M, et al.2006. Characterization of the oligosaccharide component of alpha3beta1 integrin from human bladder carcinoma cell line T24 and its role in adhesion and migration. Eur J Cell Biol, 85:47-57
Poruchynsky MS,Wang EE,Rudin CM,et al. 1998.Bcl-xl is Phosphorylated in malignant cells following microbutule disruption. Caneer Res,58:3331-8
Poupot M, Pont, F. Fournie JJ. 2005.Profiling Blood Lymphocyte Interactions with Cancer Cells Uncovers the Innate Reactivity of Human gamma delta T Cells to Anaplastic Large Cell Lymphoma.Immunol, 174:1717-1722
Prins M, Graf MR, Merchant RE, et al. 2003.Thymus Function and Output of Recent Thymus Emigrant T Cells During Intracranial Glioma Progression. Neurooncol, 64:45-54
Przybylo M, Litynska A, Pochec E. 2005. Different adhesion and migration properties of human HCV29 non-malignant urothelial and T24 bladder cancer cells: role of glycosylation. Biochimie, 87:133-142
Przybylo M, Martuszewska D, Pochec E,et al.2007. Identification of proteins bearing beta1-6 branched N-glycans in human melanoma cell lines from different progression stages by tandem mass spectrometry analysis.Biochim Biophys Acta, 1770:1427-1435
Raff M. 1998.Cell suicide for beginners.Nature,396:119-22
Ralphs MH, Creamer R, Baucom D,et al.2008. Relationship between the endophyte Embellisia spp. and the toxic alkaloid swainsonine in major locoweed species (Astragalus and Oxytropis).J Chem Ecol, 34:32-38
Redipe O, Furbert-Harris OA, Laniyan PM, et al. 2003.Enhanced proliferation of functionally competent bone marrow cells in different strains of mice treated with swainsonine . Int Immunophamacol, 3(3):445-455
Scatena CD,Stewart ZA,Mays D,et al. 1998.Mitotic Phosphorylation of Bcl-2 during Normal Cell Cycle Progression and Taxol-induced Growth arrest.The journal of biological chemistry,46:30777 -30784
Schneider MJ, Ungemach FS, Broquist HP, et al. 1983.IS,.2R,8R,8aR)-1,2,8- Trihydroxyoctahydroindoli- zidine (swainsonine), an a-mannosidase inhibitor from Rhiocronia Leguminicola. Tetrahedron,29:22
Semenza GL, Hypoxia. 2000.Clonal selection, and the role of HIF-1 in tumor progression. Crit- Revbiochem-Mol-bio, l35(2):71-103
Shanker A, Singh SM.2003.Immunopotentiation in Mice Bearing a Spontaneous Transplantable T-cell Lymphoma: Role of Thymic Extract.Neoplasma, 50:272-279
Shi Y. 2001.A view of mitochondria-mediated apoptosis.Nat Struct Biol,8:394
Steven WH. 1998. To die or not to die: an overview of apoptosis and its role in disease. JAMA-Journal of the American Medical Association, 279:300-307
Subhash C. Gautam I. 1998. Nonselective inhibition of proliferation of transformed and nontransformed cells by the anticancer agent curcumin (diferuloylmethane) . Biochemical Pharmacology, 55:1333-1339
Sugikawa E, Hosoi T, Yazaki N, et al. 1999.Mutant p53 mediated induction of cell cycle arrest and apoptosis at G1 phase by 9-hydroxyellipticine. Anticancer Research, 19(413):3099
Sun JY, Yang H, Miao S, et al. 2009. Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo.Phytomedicine 16:1070-1074
Sun JY, Zhu MZ, Wang SW, et al. 2007. Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine.Phytomedicine, 14:353-359
Suzuki O, Abe M. 2008. Cell surface N-glycosylation and sialylation regulate galectin-3-induced apoptosis in human diffuse large B cell lymphoma.Oncol Rep, 19:743-748
Suzuki O, Nozawa Y, Abe M. 2006. The regulatory roles of cell surface sialylation and N-glycans in human B cell lymphoma cell adhesion to galectin-1.Int J Oncol, 28:155-160
Tong D, Mu P, Dong Q, et al. 2007. Immunological evaluation of SW-HSA conjugate on goats. Colloids Surf B Biointerfaces, 58:61-67
Tulsiani DRP, Broquist HP, James LF, et al. 1984.The similar effects of swainsonine and locoweed on tissue giycosidases and oligosaccharides of the pig indicate that the alkaloid is the pricipal toxin responsible for the induction of locoism. Arch, Biochem. Biophys, 232:76-85
Valdez Barillas JR,Paschke MW,Ralphs MH, et al.2007. White locoweed toxicity is facilitated by a fungal endophyte and nitrogen-fixing bacteria.Ecology, 88:1850-1856
Vaux DL,Strasser A. 1996.The molecular biology of apoptosis. Pro natl Acad Sci USA,93:2239-44 W. Hadden. 2003.Immunodeficiency and Cancer Prospects for Correction. Int Immunopharmacol, 3:1061-1071
Warrant CD, Daniel PF, Bugge B, et al. 1988. The structure of oligosacchariges excreated by sheep with swainsonine toxicosis. J. of Biol . Chem, 263 (29):15041-15049
Yeung TK. 1999.The mode of action of taxol: apoptosis at low concentration and necrosis at high concentration. Biochemical Biophysical Research Communication, 263(2):398-402
Yi HL,Carmen T,Roman PS. 1998.Phosphorylation of Bcl-2 is a marker of M Phase Events and Not a Determinant of Apoptosis.The Joural of Biological Chemistry,273(30):18984-91
Yoshida T, Zhang Y, Rivera Rosado LA, et al. 2009. Repeated treatment with subtoxic doses of TRAIL induces resistance to apoptosis through its death receptors in MDA-MB-231 breast cancer cells.Mol Cancer Res, 7:1835-1844
Yoshikawa M.1999.Glycyrrhizin inhibits TNF-induced, but not fas-mediated apoptosis in the human hepatoblastoma line HepG2. Biological Pharmaceutical Bulletin, 22(9):951-953
Zhao X, Cui Z, Geng G, et al. 2007.Determination of swainsonine in A. variabilis bunge by gas chromatography with methyl-alpha-D-mannopyranoside internal standard method.Se Pu, 25:781-782
Zhao XH, He X, Wang JN.2009. Biodegradation of Swainsonine by Acinetobacter calcoaceticus strain YLZZ-1 and its isolation and identification. Biodegradation, 20:331-338
Zhou GF, Sun YP, Xin H, et al. 2004. In vivo antitumor and immunomodulation activities of different molecular weight lambda-carrageenans from Chondrus ocellatus. Pharmacological Research, 50:47-53
白洁. 2005.苦马豆素制备的研究进展.邯郸学院学报,15(3):66-68
曹光荣,赵宝玉,王凯. 1998.英得尔种羊场采用轮牧法预防棘豆中毒试验初报.动物毒物学,1-2:38-40
曹世龙. 2001.肿瘤学新理论与新技术.人民军医出版社
陈德坤,雷莉辉,郭战军,等. 2003.甘肃棘豆生物碱对小鼠外周血免疫细胞活性及数量的影响.中国兽医科技,33(5):34-36
陈东鸿,贺平. 1998.柴胡及甘草酸对小鼠肝细胞凋亡的影响.第四军医大学学报,19(3):279-280
陈丽娟,盛瑞兰,汪承亚,等.1998.AO/EB荧光染色法测定阿糖胞苷诱导HL-60细胞凋亡.中华血液学杂志,19(1):41-42.
陈绍淑,赵宝玉,高睿,等.2004.苦马豆素的免疫原性及抗肿瘤研究进展.天然产物研究与开发,16(1):66-70
陈绍淑,赵宝玉,何生虎,等. 2004.小鼠小花棘豆生物碱中毒的病理学观察.中国兽医科技,34(12):77-79
陈智超,李秋柏,邵菁,等. 2006.小白菊内酯对多发性骨髓瘤细胞的生长抑制及其凋亡诱导作用.中华医学杂志,86(28):1993-1996
戴卉敏,杨鸣琦,李锡杰,等. 2009.豆类丝核菌培养液中苦马豆素分离提取.安徽农业科学,37(28):13440-13440
戴林. 1996.增殖细胞核抗原与胃癌.国外医学-消化系疾病分册,16(1):3-5
丁伯良,王建辰,薛登民,等. 1995.奶山羊甘肃棘豆中毒卵巢、胎盘的病理学研究.中国兽医学报, 15(1):27-32
丁伯良,王建辰. 1994.甘肃棘豆对山羊精子形态和超微结构的影响.西北农业大学学报,22(2):44-49
丁志山,高承贤,陈铌铍,等. 2003.姜黄素具有抑制血管生成与诱导肿瘤细胞凋亡双重作用.中国药理学通报,19(2):171-173
方乐堃，潘凌霄，黎雅婷，等.2007.复方小柴胡汤对荷EAC鼠IL-2水平和CD4+/CD8+比值的影响.中国病理生理杂志,23(9):1720-1723
高冬,高永琳,白平. 2003.半枝莲对宫颈癌细胞钙信号系统的影响.中药材,26(10):730-733
葛金文,陈大舜. 1997.细胞凋亡在中医药研究中的地位.湖南中医学院学学报[J],17(3):68-70
苟晨,刘文明,童德文.2008. 3种苦马豆素人工抗原的合成及其免疫原性研究.西北农业学报,17(3):28-32
顾百群,曹光荣,薛登民. 1991.山羊甘肃棘豆中毒治疗初探.畜牧兽医杂志,2:11-14
郭小琴. 1997.口服补液盐对绒山羊棘豆草中毒的疗效.中国兽医科技,27(12):44
黄秀梅,李波. 2003.氧化苦参碱对TNFα、IL26和IL28的影响.中成药,25(11):903-906
黄益玲,黄利鸣,石新兰,等. 2005.天花粉蛋白对人宫颈癌HeLa细胞增殖和细胞调亡的影响.中国药理学通报,21(2):253-254
霍星华,赵宝玉,王建军,等. 2008.镰形棘豆化学成分预试及生物碱成分薄层色谱分析.西北农业学报,17(2):24-28,32
金伯泉. 2001.细胞和分子免疫学.北京:科学出版社,695-704
孔庆志,黄冬生,黄涛,等. 2003.三种中药注射剂对小鼠移植性S180肉瘤血管形成的抑制作用.中国医院药学杂志,23(11):646-648
孔庆志,黄涛,黄冬生,等. 2003.苦参素对小鼠移植性S180肉瘤血管形成的抑制作用.中国药师, 6(12):769-771
李建科,刘诩中,卢建雄,等. 1995.甘肃棘豆饲喂小白鼠的亚慢性毒性效应及安全利用研究.中国兽医科技,25(8):28-30
李建科,杨具田,卢建雄,等. 1997.甘肃棘豆草粉对肥育猪的效果和毒性试验.中国兽医科技,27(5):30-31
李建科. 1997.中国棘豆属植物开发利用研究现状及前景评述.草与畜杂志,4:3-5
李立,赵俊,刘文明,等. 2008.苦马豆素-HSA对小鼠免疫原性研究.西北农林科技大学学报(自然科学版),36(1):23-27
李嫔,田国才,林娜,等. 1998.广枣总黄酮对小鼠胸腺细胞凋亡及腺苷脱氧酶(ADA)活性的影响.中华微生物和免疫学杂志,18(6):386-391
李勤凡,王建华,刘志斌,等. 2005.萃取法提取甘肃棘豆中的苦马豆素研究初报.中国农学通报,21(5):143-145
李晓光,谢锦玉,李文梅. 1998.大蒜油诱导人胃癌细胞分化和凋亡的机制研究.中华肿瘤杂志,20(5):325-327
李锡杰,杨鸣琦,张伟,等. 2009.金龟子绿僵菌中苦马豆素的提取.精细化工,6:554-557
梁冰,颜世芬,陈茂齐,等. 1994.甘肃棘豆挥发性成分研究Ⅰ.精油成分分离与鉴定.分析测试学报, 13(1):37-43
梁克明,谢艳华,石梅,等. 2002.九节龙皂甙对Hela细胞生长的抑制作用.第三军医大学学报,24(6):725-728.
刘炳亚,林言箴. 1998.苦马豆素抑制胃癌生长及转移的试验研究.中华肿瘤杂志, 20(3):168-170
刘复生,刘彤华.1997.肿瘤病理学.北京:北京医科大学-中国协和医科大学联合出版社
刘铭,王明娟,刘伟,等. 2008.甘肃棘豆体内生物碱部位活性的研究.中国现代医药杂志,10(12):8-11
刘秋燕,吕占军,何小波,等. 2004.雷公藤内酯醇对人宫颈癌细胞的凋亡诱导效应.中国肿瘤生物治疗杂志,1l(1):36-38
刘巍,张晓彬,李雅,等.2006.苦马豆素的抑瘤和免疫增强作用.西北药学杂志,21(6):258-260
刘伟,张毓,王溪,等. 2008.植物生长季节不同栖息地高原鼠兔的食物选择.兽类学报,28(4):358-366
刘志滨,赵兴华,余永涛,等. 2006.甘肃棘豆中苦马豆素提取工艺改进初报.西北农林科技大学学报(自然科学版),34(1):97-99,104
路浩,王建军,孙莉莎,等. 2009.苦马豆素抗肿瘤作用研究进展.动物医学进展,30(9):87-90
卢萍,赵萌莉,韩国栋,等. 2006.内蒙古疯草及其研究进展.中国草地学报,28(1):63-68
马寿福,刁治民,张静,等. 2007.棘豆属毒草防治及开发利用.青海草业,16(2):33-37
马晓华,沃兴德,梁海曼. 1999.姜黄素抗肿瘤作用与诱导肿瘤细胞凋亡的研究概况.国外医学-肿瘤学分册,26(1):21-23
孟协中,张如明. 1995.甘肃棘豆中有毒生物碱的研究.草业学报,4(1):6-8
潘子民,叶大风,谢幸,等. 2002.人参皂甙Rg3对荷卵巢癌的严重联合免疫缺陷鼠的抗肿瘤血管生成作用的研究.中华妇产科杂志,37(4):227-230
彭黎明. 1999.吞噬细胞对凋亡细胞的识别与吞噬.中华护理学杂志,28:304-306
钱红兰,胡倩,胡旭东,等.2007.槐耳浸膏对骨髓瘤细胞增殖和凋亡的影响.中国热带医学,7(6):889-890
芮菊生,杜懋琴,陈海明,等. 1980.组织切片技术.上海:人民教育出版社
沈明华,莫重辉,赵宝玉,等.2010.家兔实验性甘肃棘豆中毒的临床症状和病理形态学观察.动物医学进展,31(1):44-49
施新猷. 1989.医用试验动物学.西安:陕西科学技术出版社
史志诚. 1996.中国草地重要有毒植物.北京:中国农业出版社
衰静,肖余. 1996.槲皮素抗肿瘤作用研究进展.国外医学-中医中药分册,18(4):3-5
税媛媛,刘文明,赵献军,等. 2007.4种偶联率的苦马豆素-HSA合成及其对小鼠免疫原性研究.西北农业学报,16(6):1-7
宋晓凯. 2004.天然药物化学.北京:化学工业出版社
苏长青,龚西渝.1996.细胞凋亡的形态特点及生物学意义.临床与试验病理学杂志,12(4):346-348
田菲,贾英杰,陈军,等. 2003.肺一丸对肺癌血管生成及转移影响的试验研究.天津中医药,20(5):56-58
童德文,曹光荣,耿果霞,等. 2003.薄层扫描测定5种疯草中苦马豆素含量.中国兽医学报,23(2):183-184
童德文,曹光荣,李绍君. 2001.甘肃棘豆中苦马豆素的分离与鉴定.西北农林科技大学学报(自然科学版),29(3):5-7
童德文,曹光荣,赵献军. 2001.HPLC分离甘肃棘豆中苦马豆素.西北农业学报,10(2):6-8
童德文,董强,刘文明,等. 2006.苦马豆素-BSA接种山羊的免疫学研究.中国兽医杂志,42(7):15-17
童德文,董强,赵宝玉,等. 2006.用甘肃棘豆草粉饲喂苦马豆素-BSA免疫山羊的血清相关酶分析.中国兽医科学,36(4):331-335
童德文,董强,赵宝玉,等. 2006.苦马豆素-BSA免疫山羊的血清相关酶评价.中国农业科学,39(11):2384-2389
童德文,赵宝玉,廉士刚,等. 2004.甘肃棘豆化学成分研究Ⅰ.碱水氯仿提取部位成分分析.中兽医医药杂志,23(5):13-16
王汉斌,庞琦,富壮,等.2010.雄黄体外诱导C6胶质瘤细胞凋亡的特点及分析.山东大学学报(医学版),1:21-24,29
王建军,赵宝玉,万学攀,等. 2008.苦马豆素的分离及其体外抗肿瘤作用.中国兽医杂志,44(2):70-71
王凯,莫重辉,赵宝玉,等. 1999.“棘防E号”预防绵羊甘肃棘豆中毒.畜牧与兽医,31(3):31-32
王凯. 1998.“棘防A号”试验性预防山羊甘肃棘豆中毒.中国兽医科技,28 (8):31-32
王明娟,刘铭,刘伟,等. 2009.甘肃棘豆生物碱部位体内抗肿瘤作用及对免疫功能的影响.中国中西医结合杂志,29(11):1009-1011
王银朝,赵宝玉,樊月圆,等. 2005.甘肃棘豆中苦马豆素的分离与鉴定.动物医学进展,1:8-10
沃兴德,丁志山,尹丽慧,等. 2003.参麦对小鼠移植瘤组织中bFGF和MMP-2表达的影响.肿瘤防治杂志,10(4):345-347
吴达,龙玲,张彦明. 2007.甘肃棘豆抗肿瘤活性成分的筛选.中国兽医科学,37(5):440-443
吴旭锦,杨鸣琦,白春黎,等.2005.苦马豆素的来源及分离方法进展.动物医学进展,26(5):41-44
伍银桥,王孟薇,吴本俨,等. 2003.胃癌前病变演变过程中凋亡相关蛋白和PCNA的表达意义.世界华人消化杂志,11(8):1219-1222
吴振,吴立军,田代真一,等. 2004.紫草素诱导HeLa细胞凋亡经过caspase激活的机制.中国药理学通报,20(5):540-544
夏凤琴,李延钩. 1996.细胞凋亡.国外医学-老年病学分册,17(3):123-125
肖东,顾振纶. 1998.槲皮素下调人白血病HL60细胞bcl-2基因表达.中国药理学报, 19(6):551-553
徐超,刘斌,石任兵.2008.棘豆属植物化学成分与药理作用.国外医药(植物药分册),23(1):1-7
徐叔云,卞如濂,陈修. 1991.药理试验方法学(第二版).北京:人民卫生出版社
徐中平,李福川,王海仁. 1999.昆布多糖硫酸酯的抑制血管生成和抗肿瘤作用.中草药,30(7):551-553
薛妍,夏天,赵建斌,等. 2000.姜黄素对人肝癌细胞SMMC-7721的抑制作用.第四军医大学学报,25(5):84-86
杨鸣琦,曹光荣,李绍君. 1998.苦马豆素对小白鼠移植性肿瘤S180、ARS的抑制试验.动物医学进展,19(2):26-29
叶思杰,刘建利,黄伟平.2009.抗癌天然产物苦马豆素的合成研究进展.有机化学,29(5):689-695
于珊,秦宝福. 2006.苦马豆素国内外研究进展.中国农村小康科技,6:63-67
余谦,李庆明,吴伟康,等. 2000.中药胃康宁对试验性胃癌PCNA、P53蛋白表达的干预作用.中山医科大学学报,21(10):1-7
余永涛,耿果霞,刘志滨,等. 2006.家畜毛瓣棘豆中毒研究.草业科学,23(5):75-77
曾文军,王柳均. 2005.细胞凋亡的流式细胞仪检测技术研究进展.Anthology of Medicine,24(3):425-428
张芳芳,杨光明,王栋,等.2010.镰形棘豆提取物抗肿瘤活性的体外实验研究.药学与临床研究,18(2):135-138
张生民,高其东,侯德慧,等. 1981.甘肃棘豆中毒.畜牧兽医学报,12(3):145-149
张守信,曹光荣,李绍君,等. 1992.甘肃棘豆醇提物对小鼠移植性肿瘤S37 H22的抑制试验.畜牧兽医杂志,2:13-15
张为民,蒲鹏,张德刚,等. 2005.从苦豆子种子中提取生物碱的方法研究.中国农学通报,21(2):7-9
张莹,张起辉,吴立军,等.2004.吴茱萸碱诱导人宫敬癌Hela细胞凋亡过程中非caspase调控因素.中国药理学通报,20(1):61-64
张志敏,王建华,赵兴华,等.2008.苦马豆素对小鼠腹腔巨噬细胞免疫功能的影响.中国农业科学,41(10):3422-3428
赵宝玉,曹光荣,童德文,等.“棘防C”预防山羊甘肃棘豆中毒初探.动物医学进展,1999,20(1):42-44
赵宝玉,王凯,曹光荣,等. 2001.甘肃棘豆毒性生物碱研究.中国兽医学报,21(2):173-176
赵宝玉,陈绍淑,莫重辉,等.2005.苦马豆素的提取分离及其抗肿瘤活性研究.毒理学杂志, 19(A03):252
赵敬,赵涌.2004.姜黄素对人宫颈癌细胞株Hela细胞抑制及凋亡的影响.重庆医科大学学报,29(3):296-299.
赵俊,童德文,税媛媛,等. 2006.甘肃棘豆草中苦马豆素的提取分离工艺比较研究.西北植物学报,26(7):1459-1463
周建军,乐秀芳,韩家娴,等. 1994.影响MTT方法测定结果的一些因素.肿瘤,14(2):93.
Adams JM, Cory S. 1999.The Bcl-2 Protein falllily: Arbiters of cell survival .Science, 281:1322-6.
Afshrihari C, Beuno M, Lamb P, et al. 2000.Interaction of the metastasis suppressing Proteins KAI l and E-cadherin in epithelial cells. Proc Am Assoc Cancer Res,40:197
Ajish Kumar KS, Chaudhari VD, Dhavale.2008. Efficient synthesis of (+)-1,8, 8a-tri- epi-swainsonine, (+)-1,2-di-epi-lentiginosine,(+)-9a-epi-homocastanospermine and (-)-9-deoxy-9a-epi- homocastanosper -mine from a D-glucose-derived aziridine carboxylate, and study of their glycosidase inhibitory activities. Org Biomol Chem, 6:703-711
Arakaki N, Kazi JA, Kazihara T, et al. 1998.Hepatocyte growth factor/scatter factor activates the apoptosis signaling pathway by increasing caspase-3 activity Sarcoma 180 cells. Biochemical and Biophysical Research Communication, 245:211-215
Ashley AK,Custis M, Ashley R, et al. 2006. Toxicokinetic profile of swainsonine following exposure to locoweed (Oxytropis sericea) in naive and previously exposed sheep. N Z Vet J, 54:34-40
Au CW, Pyne SG. 2006. Asymmetric synthesis of anti-1,2-amino alcohols via the Borono-Mannich reaction: a formal synthesis of (-)-swainsonine. J Org Chem, 71:7097-7099
Bates RW, Dewey MR. 2009. A formal synthesis of swainsonine by gold-catalyzed allene cyclization. Org Lett, 11:3706-3708
Bi J,Aggarwal VK. 2008.Application of furyl-stabilized sulfur ylides to a concise synthesis of 8a-epi- swainsonine. Chem Commun (Camb), 120-122
Call JA, Eckhardt SG, Camidge DR. 2008. Targeted manipulation of apoptosis in cancer treatment. Lancet Oncol ,9 :1002-1011
Caroline D, Scatena S. 1998. Mitotic phosphorylation of bcl-2 during normal cell cycle progression and taxol-induced growth arrest. Journal of Biological Chemistry, 273(46):30777-30781
Ceccon J, Greene AE, Poisson JF. 2006. Asymmetric [2 + 2] cycloaddition: total synthesis of (-)- swainsonine and (+)-6-epicastanospermine. Org Lett, 8:4739-4742
Chipuk JE, Kuwana T, Bouchier-Hayes L, et al. 2004.Direct activation of bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science, 303:1010-1014
Chooprayoon S, Kuhakarn C, Tuchinda P, et al. 2010.Asymmetric total synthesis of (+)-swainsonine. Org Biomol Chem
Christine D, Pozniak CD, Radinovic S, et al. 2000.An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science, 289(14):304-306
Colegate SM, Dorling PR, Huxtable CR. 1979.A spectroscopic investigation of swainsonine: an a mannosidase inhibitor isolated from Swainsina canecens. Aust. J. Chem,32:2257-2264
D. Mumberg PA, Monach S,Wanderling M, et al. 1999. CD4+ T Cells Eliminate MHC Class II-negative Cancer Cells in Vivo by Indirect Effects of IFN-γ. Immunology, 96:8633-8638
Dantas AF, Riet-Correa F, Gardner DR, et al. 2007. Swainsonine-induced lysosomal storage disease in goats caused by the ingestion of Turbina cordata in Northeastern Brazil. Toxicon,49:111-116
Fei XF, Wang BX, Li TJ, et al. 2003.Evodiamine, a constituent of Evodiae fructs, induces anti-proliferating effects in tumor cells. Cancer Science, 94:92-98
Gao XH, Xu YX, Janakiraman N, et al. 2002. Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production. Biochemical Pharmacology, 62:1299-1308
Goss PE, Baptiste J, Fernandes B, et al. 1994. A phase I study of swainsonine in patients with advanced malignancies. Cancer Res, 54:1450-1457
Goss PE, Reid CL, Bailey D, et al. 1997. Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. Clin Cancer Res, 3:1077-1086
Grooss A, McDonnell JM, Korsmeyer SJ. 1999.Bcl-2 family members and the mitochondria in apoptosis. Genes Development, 13:1899-1911
Guo H, O'Doherty GA. 2006. De novo asymmetric synthesis of D- and L-swainsonine. Org Lett, 8:1609-1612
Guo H, O'Doherty, GA. 2008. De Novo Asymmetric Syntheses of d-, l- and 8-epi-Swainsonine. Tetrahedron , 64:304-313
Hafez SA, Caceci T, Freeman, et al. 2007.Angiogenesis in the caprine caruncles in non-pregnant and pregnant normal and swainsonine-treated does. Anat Rec (Hoboken), 290:761-769
Han SC,Yee K,Taeseok B, et al. 2006. Enhancement of Antitumor Immunity of Dendritic Cells Pulsed with Heat-treated Tumor Lysate in Murine Pancreatic Cancer. Immunol Lett, 103:142-148
Harris MH,Thompson CB. 2000.The role of the Bcl-2 family in the regulation of outer Mitochondrial membrane permeability.Cell Death Differ, 7:1182-91.
Hendrikse AS, Hunter AJ, Keraan M, et al. 2000. Effects of low dose irradiation on TK6 and U937 cell: induction of p53 and its role in cell-cycle delay and the adaptive response. International Journal of Radiation Biology, 76(1):11
Hengartner MO. 2000.The biochemistry of apoptosis.Nature, 407:770-6
Hueza IM, Guerra JL, Haraguchi, et al.2007. Assessment of the perinatal effects of maternal ingestion of Ipomoea carnea in rats. Exp Toxicol Pathol, 58:439-446
James LF, Panter KE.1991.Swainsonine-induced high mountain disease in calves. Vet. Hum. Toxicol, 33(3):217-219
Jens BH, Seiichi N, Ray M, et al. 2000. Oral administration of an estrogen metabolite-induced potentiation of radiation antitumor effects in presence of wild-type p53 in non-small-cell lung cancer. International Journal of Radiation Oncology Biology Physics, 48:1127-1137
Joza N,Susin SA,Daugas E,et al. 2001. Essential role of the mitochondrial apoptosis-inducing factor in Programmed cell death.Nature,410:549-54
Kerr JFR, Wyllie AH, Currie AR. 1972. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer, 26:239
Korbakis D, Scorilas A. 2009. Treatment of gastric cancer cells with 5-fluorouracil/leucovorin and irinotecan induces distinct alterations in the mRNA expression of the apoptosis-related genes, including the novel gene BCL2L12. Tumour Biol , 30:100-107
Kuo ML.1996.Curcumin, an antioxidant and antitumor promoter, induces apoptosis in human leukemia cells. Biochemical Biophysical Acta, 1317(2):95-99
Li S, Chien S, Branemark PI. 1999. Heat shock-induced necrosis and apoptosis in osteoblasts. Journal of Orthopaedic Research, 17:891-899
Lin XD, Han C. 2000. Gap junctional communication and the tyrosine phosphorylation of connexin 43 in interaction between breast cancer and endothelial cells. World Journal of Gastroenterology, 6(5):699-703
Litynska A, Przybylo M, Pochec E, et al.2006. Does glycosylation of melanoma cells influence their interactions with fibronectin? Biochimie, 88:527-534
Maiden GH. 1901.Plants reputed to the poisnous to livestock in Australia. Dept. Agric, NSW, Misc. Publi, 10447
Majno G, Joris I. 1995.Apoptosis,oncosis,and necrosis,an overview of cell death.Am J Pathol, 146(l):3-15
Marsh CD. 1909.The locoweed disease of the plains. U.S. Department of Agriculture, Bureau of Animal Industry, Washington, D.C,1-130
Molyneux RJ, James LF, Panter KE. 1984. Chemistry of toxic consriruents of locoweed (Astragalus and Osytropis) species. Symposium, Plant Toxicology, Queensland, Austalia,The ueensland Poisnous Plants Committee, 266-278
Nagata S. 2000.Apoptotic DNA fragmentation. Exp.Cell Res, 10:12-18
Nakazawa Y, Kamijo T, Koike K, et al. 2003.ARF tumor suppressor induces mitochondria-dependent apoptosis by modulation of mitochondrial bcl-2 family proteins. Journal of Biological Chemistry, 278(30):27888-27895
Opez V, Charyulu B. 2002.Influence of Breast Cancer on Thymus Function in Mice. J Mammary Gland Biol Neoplasia, 7:191-199
Pataer A, Fanale MA, Roth JA, et al.2006. Induction of apoptosis in human lung cancer cells following treatment with amifostine and an adenoviral vector containing wild-type p53. Cancer Gene Ther 13, 806-814
Perl AK, Petra W, Ulf D. 1998.Acausal role for E-cadherin in the transition from adenoma to carcinoma. Nture, 392(l):190-193
Pochec E, Litynska A, Bubka M, et al.2006. Characterization of the oligosaccharide component of alpha3beta1 integrin from human bladder carcinoma cell line T24 and its role in adhesion and migration. Eur J Cell Biol, 85:47-57
Poruchynsky MS,Wang EE,Rudin CM,et al. 1998.Bcl-xl is Phosphorylated in malignant cells following microbutule disruption. Caneer Res,58:3331-8
Poupot M, Pont, F. Fournie JJ. 2005.Profiling Blood Lymphocyte Interactions with Cancer Cells Uncovers the Innate Reactivity of Human gamma delta T Cells to Anaplastic Large Cell Lymphoma.Immunol, 174:1717-1722
Prins M, Graf MR, Merchant RE, et al. 2003.Thymus Function and Output of Recent Thymus Emigrant T Cells During Intracranial Glioma Progression. Neurooncol, 64:45-54
Przybylo M, Litynska A, Pochec E. 2005. Different adhesion and migration properties of human HCV29 non-malignant urothelial and T24 bladder cancer cells: role of glycosylation. Biochimie, 87:133-142
Przybylo M, Martuszewska D, Pochec E,et al.2007. Identification of proteins bearing beta1-6 branched N-glycans in human melanoma cell lines from different progression stages by tandem mass spectrometry analysis.Biochim Biophys Acta, 1770:1427-1435
Raff M. 1998.Cell suicide for beginners.Nature,396:119-22
Ralphs MH, Creamer R, Baucom D,et al.2008. Relationship between the endophyte Embellisia spp. and the toxic alkaloid swainsonine in major locoweed species (Astragalus and Oxytropis).J Chem Ecol, 34:32-38
Redipe O, Furbert-Harris OA, Laniyan PM, et al. 2003.Enhanced proliferation of functionally competent bone marrow cells in different strains of mice treated with swainsonine . Int Immunophamacol, 3(3):445-455
Scatena CD,Stewart ZA,Mays D,et al. 1998.Mitotic Phosphorylation of Bcl-2 during Normal Cell Cycle Progression and Taxol-induced Growth arrest.The journal of biological chemistry,46:30777 -30784
Schneider MJ, Ungemach FS, Broquist HP, et al. 1983.IS,.2R,8R,8aR)-1,2,8- Trihydroxyoctahydroindoli- zidine (swainsonine), an a-mannosidase inhibitor from Rhiocronia Leguminicola. Tetrahedron,29:22
Semenza GL, Hypoxia. 2000.Clonal selection, and the role of HIF-1 in tumor progression. Crit- Revbiochem-Mol-bio, l35(2):71-103
Shanker A, Singh SM.2003.Immunopotentiation in Mice Bearing a Spontaneous Transplantable T-cell Lymphoma: Role of Thymic Extract.Neoplasma, 50:272-279
Shi Y. 2001.A view of mitochondria-mediated apoptosis.Nat Struct Biol,8:394
Steven WH. 1998. To die or not to die: an overview of apoptosis and its role in disease. JAMA-Journal of the American Medical Association, 279:300-307
Subhash C. Gautam I. 1998. Nonselective inhibition of proliferation of transformed and nontransformed cells by the anticancer agent curcumin (diferuloylmethane) . Biochemical Pharmacology, 55:1333-1339
Sugikawa E, Hosoi T, Yazaki N, et al. 1999.Mutant p53 mediated induction of cell cycle arrest and apoptosis at G1 phase by 9-hydroxyellipticine. Anticancer Research, 19(413):3099
Sun JY, Yang H, Miao S, et al. 2009. Suppressive effects of swainsonine on C6 glioma cell in vitro and in vivo.Phytomedicine 16:1070-1074
Sun JY, Zhu MZ, Wang SW, et al. 2007. Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine.Phytomedicine, 14:353-359
Suzuki O, Abe M. 2008. Cell surface N-glycosylation and sialylation regulate galectin-3-induced apoptosis in human diffuse large B cell lymphoma.Oncol Rep, 19:743-748
Suzuki O, Nozawa Y, Abe M. 2006. The regulatory roles of cell surface sialylation and N-glycans in human B cell lymphoma cell adhesion to galectin-1.Int J Oncol, 28:155-160
Tong D, Mu P, Dong Q, et al. 2007. Immunological evaluation of SW-HSA conjugate on goats. Colloids Surf B Biointerfaces, 58:61-67
Tulsiani DRP, Broquist HP, James LF, et al. 1984.The similar effects of swainsonine and locoweed on tissue giycosidases and oligosaccharides of the pig indicate that the alkaloid is the pricipal toxin responsible for the induction of locoism. Arch, Biochem. Biophys, 232:76-85
Valdez Barillas JR,Paschke MW,Ralphs MH, et al.2007. White locoweed toxicity is facilitated by a fungal endophyte and nitrogen-fixing bacteria.Ecology, 88:1850-1856
Vaux DL,Strasser A. 1996.The molecular biology of apoptosis. Pro natl Acad Sci USA,93:2239-44 W. Hadden. 2003.Immunodeficiency and Cancer Prospects for Correction. Int Immunopharmacol, 3:1061-1071
Warrant CD, Daniel PF, Bugge B, et al. 1988. The structure of oligosacchariges excreated by sheep with swainsonine toxicosis. J. of Biol . Chem, 263 (29):15041-15049
Yeung TK. 1999.The mode of action of taxol: apoptosis at low concentration and necrosis at high concentration. Biochemical Biophysical Research Communication, 263(2):398-402
Yi HL,Carmen T,Roman PS. 1998.Phosphorylation of Bcl-2 is a marker of M Phase Events and Not a Determinant of Apoptosis.The Joural of Biological Chemistry,273(30):18984-91
Yoshida T, Zhang Y, Rivera Rosado LA, et al. 2009. Repeated treatment with subtoxic doses of TRAIL induces resistance to apoptosis through its death receptors in MDA-MB-231 breast cancer cells.Mol Cancer Res, 7:1835-1844
Yoshikawa M.1999.Glycyrrhizin inhibits TNF-induced, but not fas-mediated apoptosis in the human hepatoblastoma line HepG2. Biological Pharmaceutical Bulletin, 22(9):951-953
Zhao X, Cui Z, Geng G, et al. 2007.Determination of swainsonine in A. variabilis bunge by gas chromatography with methyl-alpha-D-mannopyranoside internal standard method.Se Pu, 25:781-782
Zhao XH, He X, Wang JN.2009. Biodegradation of Swainsonine by Acinetobacter calcoaceticus strain YLZZ-1 and its isolation and identification. Biodegradation, 20:331-338
Zhou GF, Sun YP, Xin H, et al. 2004. In vivo antitumor and immunomodulation activities of different molecular weight lambda-carrageenans from Chondrus ocellatus. Pharmacological Research, 50:47-53
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |