五种天然有效部位生物总碱的提取分离及体外抗肿瘤作用研究
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摘要
恶性肿瘤严重威胁着人类生命和健康。手术、化疗和放疗是肿瘤治疗的三大手段,其中化疗在肿瘤多学科、多手段的综合治疗中发挥着举足轻重的作用。然而肿瘤化疗在一定程度上仍有其局限性,如对肿瘤细胞的特异性抑制作用不强,毒副反应较大等。中医药作为我国的传统医学,在恶性肿瘤综合治疗中有着独特的优势。大量临床实践表明,中医药在提高恶性肿瘤的临床疗效、改善生活质量方面,发挥着越来越重要的作用。中药大多来源于植物,随着回归自然热潮的兴起,从中药(传统植物药)中挖掘和开发具有高效、低毒、廉价、广谱的天然抗肿瘤药物成为研究的热点。研究发现中药所含的多种成分均有不同程度的抗肿瘤作用,如生物碱类(长春碱、喜树碱)、二萜类化合物(紫杉醇、冬凌草甲素)。已经证实中药黄连、吴茱萸、苦参等具有较显著的抗肿瘤作用,其生物碱类成分为其主要成分。随着现代药物提取分离纯化手段的不断升级,从传统中药中寻找抗肿瘤作用的有效成分和有效部位,并在此基础上研制抗肿瘤新药具有巨大的潜力和发展前景。
[目的]
1.比较三种不同提取工艺：水提、醇提、酸提方法对吴茱萸、黄连、苦参、延胡索、钩藤有效部位—生物总碱的分离提取；得出相应最佳提取工艺。
2.利用HPLC对五种天然有效部位—生物总碱中所含有效成分进行含量测定。
[方法]
1.分别采用水提法、醇提法、酸提法三种不同提取工艺提取吴茱萸、黄连、苦参、延胡索、钩藤,制备得到相应有效部位—生物总碱；比较得出相应最佳提取工艺。
2.利用高效液相色谱仪HPLC对生物总碱中所含相应有效成分进行含量测定。
[结果]
1.三种提取工艺分离、提取五种天然抗肿瘤有效部位—生物总碱含量的比较：醇提法>酸提法>水提法
2.HPLC检测五种天然有效部位—生物总碱中相应有效成分含量的比较：
①延胡索总碱(延胡索乙素/总碱)：醇提>酸提>水提
②黄连总碱(盐酸小檗碱/总碱)：醇提>酸提>水提
③吴茱萸总碱(吴茱萸次碱/总碱)：酸提>水提>醇提
④苦参总碱：醇提>酸提>水提氧化苦参碱/总碱：醇提>酸提>水提苦参碱／总碱：水提>酸提>醇提
⑤钩藤总碱：未能精确测定其所含钩藤碱、异钩藤碱的含量
[目的]
考察水提法、醇提法、酸提法提取分离得到的吴茱萸、黄连、苦参、延胡索、钩藤五种生物总碱对人源胃癌细胞株的体外增殖抑制作用,比较得出抑制率最强的生物总碱。考察有效部位生物总碱与相应有效成分对人源胃癌细胞株抗肿瘤活性的比较。
[方法]
1.生物总碱的制备：采用水提、70%乙醇提取、1%醋酸提取法分别制备吴茱萸、黄连、苦参、钩藤、延胡索有效部位—生物总碱。
2.细胞增殖抑制实验：运用MTT法考察五种天然有效部位及相应有效成分对人源胃癌细胞株BGC-823、MKN-45的体外抗肿瘤作用。生存率=实验组OD/对照组OD×100%,抑制率=(1-实验组OD/对照组OD)×100%。
3.形态学观察：用不同浓度的吴茱萸总碱、黄连总碱、苦参总碱、钩藤总碱、延胡索总碱处理人胃癌细胞株BGC-823和MKN-45后,在倒置显微镜下观察用药组细胞形态学变化,并拍照。
[结果]
1.吴茱萸总碱、黄连总碱、苦参总碱、延胡索总碱、钩藤总碱对人源胃癌细胞MKN-45、BGC-823均有增殖抑制作用,且随着药物浓度的增加,抑制率逐渐增强,呈剂量-效应依赖关系。
2.五种生物总碱在2μg/ml-200μg/ml之间对人胃癌细胞株MKN-45抑制率比较：水提吴茱萸总碱>水提黄连总碱>醇提钩藤总碱>醇提苦参总碱>醇提延胡索总碱
①吴茱萸总碱：水提吴茱萸总碱>醇提吴茱萸总碱>酸提吴茱萸总碱
②黄连总碱：水提黄连总碱>醇提黄连总碱>酸提黄连总碱
③苦参总碱：醇提苦参总碱>水提苦参总碱>酸提苦参总碱
④延胡索总碱：醇提延胡索总碱>水提延胡索总碱>酸提延胡索总碱
⑤钩藤总碱：醇提钩藤总碱>水提钩藤总碱>酸提苦参总碱
3.有效部位生物总碱与有效成分在2μg/ml-200μg/ml之间对人胃癌细胞株MKN-45抑制率比较：水提吴茱萸总碱>吴茱萸次碱；水提黄连总碱>盐酸小檗碱醇提延胡索总碱<延胡索乙素；氧化苦参碱>醇提苦参总碱>苦参碱
4.五种生物总碱在6.25μg/ml-200μg/ml之间对人胃癌细胞株BGC-823作用48小时后,随着药物浓度的增加,抑制率逐渐增强,呈剂量-效应依赖关系。
5.水提吴茱萸总碱、水提黄连总碱、醇提苦参总碱、醇提延胡索总碱、醇提钩藤总碱在作用于胃癌BGC-823细胞48小时时,细胞生长受到明显抑制,水提黄连总碱抗肿瘤作用显著,其IC50 20.34μg/ml,不同药物浓度组间具有显著差异性。
6.细胞形态学变化：正常情况下,人胃癌细胞株BGC-823和MKN-45呈多角形,梭形,贴壁生长。在五种生物总碱的作用下,癌细胞逐渐变圆,皱缩,贴壁细胞数减少,细胞肿胀,大小不一致,细胞间隙增宽,随着药物浓度的增加,出现大量细胞碎片。
[结论]
1.吴茱萸总碱、黄连总碱、苦参总碱、钩藤总碱、延胡索总碱对人胃癌细胞株BGC-823、MKN-45体外具有较显著的增殖抑制的作用,在一定剂量范围内,呈剂量-时间依赖关系,其中水提吴茱萸总碱和水提黄连总碱对胃癌细胞株的抗肿瘤作用显著。
2.水提吴茱萸总碱、水提黄连总碱、醇提苦参总碱、醇提延胡索总碱、醇提钩藤总碱对人胃癌细胞BGC-823半数抑制的IC50分别为：25.76μg/ml、20.34μg/ml、68.51μg/ml、34.50μg/ml、33.10μg/ml。
3.水提吴茱萸总碱、水提黄连总碱较相应有效成分对人胃癌细胞增殖抑制作用强。
Cancer seriously threat to life and health of human beings. Surgery, chemotherapy and radiotherapy are the three major cancer treatment methods, including chemotherapy in cancer multidisciplinary, comprehensive treatment of multiple means to play a important role. Chemotherapy, however, to some extent still has its limitations, such as specific inhibition of tumor cells is not so obvious and toxicity. Chinese medicine as traditional medicine in China, in the treatment of malignant tumors has a unique advantage. Large number of clinical practice shows that Chinese medicine in improving the clinical efficacy of cancer and improve quality of life, playing an increasingly important role. Most traditional Chinese medicine derived from plants, with the upsurge return to nature, from the traditional Chinese medicine (traditional herbal medicine) in the excavation and development of high efficiency, low toxicity, low-cost, broad spectrum of natural antitumor drugs have become the research hotspot. Study found that Chinese herbs contain many ingredients in varying degrees of anti-tumor effects, such as alkaloids (vinblastine, camptothecin), diterpenoids (paclitaxel, oridonin). It has confimed that Chinese Coptis, Evodia and flavescens have the anti-tumor effect and their aklaloids as their major effective components. Extraction and purification of modern means of drug escalation, from natural herbal anti-tumor effect in the search for active ingredients and the active site, and on this basis, the development of cancer drugs that has tremendous potential and development prospects.
[Objective]
1.Comparison of three different extraction:aqueous extraction, ethanol extraction, acid extraction method to Evodia, Coptis, flavescens, Corydalis, Uncaria contained active site-the separation of alkaloids extracted; draw the corresponding optimum extraction method.
2.Using HPLC to determinate the effective ingredients contained in the five natural effective part of alkaloids.
[Methods]
Three diffenent extraction of aqueous extraction, ethanol extraction, acid extraction were used to isolate and extract the total alkaloids of Evodia, berberine, flavescens, Corydalis, Uncaria. The effective part of their active ingredients contained in the corresponding levels were determinated using by HPLC(high performance liquid chromatography).
[Results]
1. Three kinds of extraction of natural anti-tumor active components of the five total alkolids content of biological comparison: Ethanol extraction> acid extraction>aqueous extraction.
2. The comparison of corresponding effective ingredients in active sites extracted from five natural total alkolids measured by HPLC:
①corydalis alkaloids (Tetrahydropalmatine/total corydalis alkaloids):ethanol extraction> acid extraction> aqueous extraction.
②berberine alkaloids (berberine/total alkaloids):ethanol extraction> acid extraction> aqueous extraction.
③Evodia alkaloids (rutaecarpine/total alkaloids):acid extraction> aqueous extraction> ethanol extraction.
④Flavescens alkaloids:ethanol extraction> acid extraction> aqueous extraction Oxymatrine/alkaloids:ethanol extraction> acid extraction> aqueous extraction Matrine/alkaloids:aqueous extraction> acid extraction> ethanol extraction
⑤Uncaria alkaloids:not determined precisely contained Rhynchophylline, isorhynchophylline content, considering the result of pre-separation and extraction reagents and temperature, has a certain influence on its structural stability, leading to structural change, it is not can be measured.
[Objective]
To investigate the anti-tumor effect of five natural total alkaloids of Evodia, Coptis, flavescens, Corydalis and Uncaria extracted from three kinds extraction of aqueous extraction, ethanol extraction, acid extraction and their corresponding active ingredients contained in total alkaloids on human gastric cancer cell lines in vitro, in order to compare the strongest anti-proliferation activity of five total alkaloids. And compaere the antitumor activity of the corresponding active ingredient alkaloids and effect part of total alkaloids on human gastric cancer cell lines.
[Methods]
1. The preparation of five total alkaloids:aqueous extraction,70% ethanol extraction,1% acetic acid extraction were prepared the active site-alkaloids of Evodia, berberine, flavescens and Uncaria.
2. Cell proliferation inhibition test:Using the tetrazolium blue (MTT) to study the antitumor activities of five effect sites-total alkaloids and the natural active ingredients on human gastric cancer cells BGC-823, MKN-45 in vitro. Survival rate= (experimental group calculated OD)/(control group OD)×100%, Inhibition rate= (1-experimental OD/ control OD)×100%.
3. Morphological observation:different concentrations of Evodia total alkaloids, berberine total alkaloids, Flavescens total alkaloids, Uncaria total alkaloids and corydalis total alkaloids to treat on human gastric cancer cell line BGC-823 and MKN-45 after observed under inverted microscope Morphological changes of treated cells, and photographed.
[Results]
1. The inhibition effect of the effective part of Evodia alkaloids, berberine alkaloids, matrine alkaloids, corydalis alkaloids, Uncaria alkaloids on human gastric cancer cell line MKN-45, BGC-823 were obviously observed and with the increase in drug concentration, inhibition rate increased in a dose dependent relationship.
2. The comparison of inhibite rate of five alkaloids between the 2μg/ml-200μg/ml human gastric cancer cell line MKN-45:Evodia alkaloids aqueous> aqueous berberine alkaloids> ethanol uncaria alkaloids> ethanol matrine alkloids> ethanol corydalis alkaloids
①Evodia alkaloids:aqueous extraction>ethanol extraction>acid extraction;
②berberine alkaloids:aquesous extraction>ethanol extraction>acid extraction;
③Flavescens alkaloids:ethanol extraction>aqueous extraction>acid extraction;
④Corydalis alkaloids:ethanol extraction>aqueous extraction>acid extraction;
⑤Uncaris alkloidst:ethanol extraction>aqueous extraction>acid extraction; The comparison of inhibition rate of five natural effective part of the active component of alkaloids in 2μg/ml-200μg/ml concetration on human gastric cancer cell line MKN-45: Aqueous extract Evodia alkaloids> rutaecarpine; aqueous berberine alkaloids> berberine; Ethanol total alkaloids ethanol matrine> matrine.
3. Five alkaloids between 6.25μg/ml-200μg/ml concentration on human gastric cancer cell line BGC-823 after 48,72 hours, with time and drug concentration, inhibition rate increased gradually in a time-dose dependent manner in a certain dose range.
4. Evodia alkaloids from aqueous extraction, Berberine alkaloids from aqueous extraction, Alkaloids ethanol, ethanol total alkaloids, Uncaria alkaloids in the role of ethanol on gastric cancer BGC-823 cells 48 hours, cell growth was inhibited, and the aqueous berberine alkaloids of IC50=20.34μg/ml, different drug concentrations were significant differences between
5. Morphologic changes:under normal circumstances, human gastric cancer cell line BGC-823 and MKN-45 were polygonal, spindle, adhered to the wall. The role of alkaloids in five, the cells became round and shrunken, reduce the number of adherent cells, cell swelling, the size of inconsistency, the cell gap widened.
[Conclusion]
1. Evodia alkaloids, berberine alkaloids, Flavescens alkaloids, Uncaria alkaloids, corydalis alkaloids in vitro have a strong inhibition of proliferation on human gastric cancer cell line BGC-823 and MKN-45 in vitro, and with the dose increased the inhibiton increased. Evodia alkaloids from aqueous extraction and berberine alkaloids from aqueous extraction have a stronger inhibitory effect on gastric cancer cells.
2. Evodia alkaloids from aqueous extraction, Berberine alkaloids from aqueous extraction, Flavescens alkaloids from ethanol extraction, Corydalis alkaloids from ethanol extraction, and Uncaria alkloids from ethanol extraction on human gastric cancer cells BGC-823 inhibition, IC50:25.76μg/30.34μg/ml、68.51μg/ml、34.50μg/ml、33.10μg/ml.
3. The inhibition the proliferation of aqueous extraction Evodia alkaloids and berberine alkaloids than the corresponding active ingredients.
[目的]
1.比较三种不同提取工艺：水提、醇提、酸提方法对吴茱萸、黄连、苦参、延胡索、钩藤有效部位—生物总碱的分离提取；得出相应最佳提取工艺。
2.利用HPLC对五种天然有效部位—生物总碱中所含有效成分进行含量测定。
[方法]
1.分别采用水提法、醇提法、酸提法三种不同提取工艺提取吴茱萸、黄连、苦参、延胡索、钩藤,制备得到相应有效部位—生物总碱；比较得出相应最佳提取工艺。
2.利用高效液相色谱仪HPLC对生物总碱中所含相应有效成分进行含量测定。
[结果]
1.三种提取工艺分离、提取五种天然抗肿瘤有效部位—生物总碱含量的比较：醇提法>酸提法>水提法
2.HPLC检测五种天然有效部位—生物总碱中相应有效成分含量的比较：
①延胡索总碱(延胡索乙素/总碱)：醇提>酸提>水提
②黄连总碱(盐酸小檗碱/总碱)：醇提>酸提>水提
③吴茱萸总碱(吴茱萸次碱/总碱)：酸提>水提>醇提
④苦参总碱：醇提>酸提>水提氧化苦参碱/总碱：醇提>酸提>水提苦参碱／总碱：水提>酸提>醇提
⑤钩藤总碱：未能精确测定其所含钩藤碱、异钩藤碱的含量
[目的]
考察水提法、醇提法、酸提法提取分离得到的吴茱萸、黄连、苦参、延胡索、钩藤五种生物总碱对人源胃癌细胞株的体外增殖抑制作用,比较得出抑制率最强的生物总碱。考察有效部位生物总碱与相应有效成分对人源胃癌细胞株抗肿瘤活性的比较。
[方法]
1.生物总碱的制备：采用水提、70%乙醇提取、1%醋酸提取法分别制备吴茱萸、黄连、苦参、钩藤、延胡索有效部位—生物总碱。
2.细胞增殖抑制实验：运用MTT法考察五种天然有效部位及相应有效成分对人源胃癌细胞株BGC-823、MKN-45的体外抗肿瘤作用。生存率=实验组OD/对照组OD×100%,抑制率=(1-实验组OD/对照组OD)×100%。
3.形态学观察：用不同浓度的吴茱萸总碱、黄连总碱、苦参总碱、钩藤总碱、延胡索总碱处理人胃癌细胞株BGC-823和MKN-45后,在倒置显微镜下观察用药组细胞形态学变化,并拍照。
[结果]
1.吴茱萸总碱、黄连总碱、苦参总碱、延胡索总碱、钩藤总碱对人源胃癌细胞MKN-45、BGC-823均有增殖抑制作用,且随着药物浓度的增加,抑制率逐渐增强,呈剂量-效应依赖关系。
2.五种生物总碱在2μg/ml-200μg/ml之间对人胃癌细胞株MKN-45抑制率比较：水提吴茱萸总碱>水提黄连总碱>醇提钩藤总碱>醇提苦参总碱>醇提延胡索总碱
①吴茱萸总碱：水提吴茱萸总碱>醇提吴茱萸总碱>酸提吴茱萸总碱
②黄连总碱：水提黄连总碱>醇提黄连总碱>酸提黄连总碱
③苦参总碱：醇提苦参总碱>水提苦参总碱>酸提苦参总碱
④延胡索总碱：醇提延胡索总碱>水提延胡索总碱>酸提延胡索总碱
⑤钩藤总碱：醇提钩藤总碱>水提钩藤总碱>酸提苦参总碱
3.有效部位生物总碱与有效成分在2μg/ml-200μg/ml之间对人胃癌细胞株MKN-45抑制率比较：水提吴茱萸总碱>吴茱萸次碱；水提黄连总碱>盐酸小檗碱醇提延胡索总碱<延胡索乙素；氧化苦参碱>醇提苦参总碱>苦参碱
4.五种生物总碱在6.25μg/ml-200μg/ml之间对人胃癌细胞株BGC-823作用48小时后,随着药物浓度的增加,抑制率逐渐增强,呈剂量-效应依赖关系。
5.水提吴茱萸总碱、水提黄连总碱、醇提苦参总碱、醇提延胡索总碱、醇提钩藤总碱在作用于胃癌BGC-823细胞48小时时,细胞生长受到明显抑制,水提黄连总碱抗肿瘤作用显著,其IC50 20.34μg/ml,不同药物浓度组间具有显著差异性。
6.细胞形态学变化：正常情况下,人胃癌细胞株BGC-823和MKN-45呈多角形,梭形,贴壁生长。在五种生物总碱的作用下,癌细胞逐渐变圆,皱缩,贴壁细胞数减少,细胞肿胀,大小不一致,细胞间隙增宽,随着药物浓度的增加,出现大量细胞碎片。
[结论]
1.吴茱萸总碱、黄连总碱、苦参总碱、钩藤总碱、延胡索总碱对人胃癌细胞株BGC-823、MKN-45体外具有较显著的增殖抑制的作用,在一定剂量范围内,呈剂量-时间依赖关系,其中水提吴茱萸总碱和水提黄连总碱对胃癌细胞株的抗肿瘤作用显著。
2.水提吴茱萸总碱、水提黄连总碱、醇提苦参总碱、醇提延胡索总碱、醇提钩藤总碱对人胃癌细胞BGC-823半数抑制的IC50分别为：25.76μg/ml、20.34μg/ml、68.51μg/ml、34.50μg/ml、33.10μg/ml。
3.水提吴茱萸总碱、水提黄连总碱较相应有效成分对人胃癌细胞增殖抑制作用强。
Cancer seriously threat to life and health of human beings. Surgery, chemotherapy and radiotherapy are the three major cancer treatment methods, including chemotherapy in cancer multidisciplinary, comprehensive treatment of multiple means to play a important role. Chemotherapy, however, to some extent still has its limitations, such as specific inhibition of tumor cells is not so obvious and toxicity. Chinese medicine as traditional medicine in China, in the treatment of malignant tumors has a unique advantage. Large number of clinical practice shows that Chinese medicine in improving the clinical efficacy of cancer and improve quality of life, playing an increasingly important role. Most traditional Chinese medicine derived from plants, with the upsurge return to nature, from the traditional Chinese medicine (traditional herbal medicine) in the excavation and development of high efficiency, low toxicity, low-cost, broad spectrum of natural antitumor drugs have become the research hotspot. Study found that Chinese herbs contain many ingredients in varying degrees of anti-tumor effects, such as alkaloids (vinblastine, camptothecin), diterpenoids (paclitaxel, oridonin). It has confimed that Chinese Coptis, Evodia and flavescens have the anti-tumor effect and their aklaloids as their major effective components. Extraction and purification of modern means of drug escalation, from natural herbal anti-tumor effect in the search for active ingredients and the active site, and on this basis, the development of cancer drugs that has tremendous potential and development prospects.
[Objective]
1.Comparison of three different extraction:aqueous extraction, ethanol extraction, acid extraction method to Evodia, Coptis, flavescens, Corydalis, Uncaria contained active site-the separation of alkaloids extracted; draw the corresponding optimum extraction method.
2.Using HPLC to determinate the effective ingredients contained in the five natural effective part of alkaloids.
[Methods]
Three diffenent extraction of aqueous extraction, ethanol extraction, acid extraction were used to isolate and extract the total alkaloids of Evodia, berberine, flavescens, Corydalis, Uncaria. The effective part of their active ingredients contained in the corresponding levels were determinated using by HPLC(high performance liquid chromatography).
[Results]
1. Three kinds of extraction of natural anti-tumor active components of the five total alkolids content of biological comparison: Ethanol extraction> acid extraction>aqueous extraction.
2. The comparison of corresponding effective ingredients in active sites extracted from five natural total alkolids measured by HPLC:
①corydalis alkaloids (Tetrahydropalmatine/total corydalis alkaloids):ethanol extraction> acid extraction> aqueous extraction.
②berberine alkaloids (berberine/total alkaloids):ethanol extraction> acid extraction> aqueous extraction.
③Evodia alkaloids (rutaecarpine/total alkaloids):acid extraction> aqueous extraction> ethanol extraction.
④Flavescens alkaloids:ethanol extraction> acid extraction> aqueous extraction Oxymatrine/alkaloids:ethanol extraction> acid extraction> aqueous extraction Matrine/alkaloids:aqueous extraction> acid extraction> ethanol extraction
⑤Uncaria alkaloids:not determined precisely contained Rhynchophylline, isorhynchophylline content, considering the result of pre-separation and extraction reagents and temperature, has a certain influence on its structural stability, leading to structural change, it is not can be measured.
[Objective]
To investigate the anti-tumor effect of five natural total alkaloids of Evodia, Coptis, flavescens, Corydalis and Uncaria extracted from three kinds extraction of aqueous extraction, ethanol extraction, acid extraction and their corresponding active ingredients contained in total alkaloids on human gastric cancer cell lines in vitro, in order to compare the strongest anti-proliferation activity of five total alkaloids. And compaere the antitumor activity of the corresponding active ingredient alkaloids and effect part of total alkaloids on human gastric cancer cell lines.
[Methods]
1. The preparation of five total alkaloids:aqueous extraction,70% ethanol extraction,1% acetic acid extraction were prepared the active site-alkaloids of Evodia, berberine, flavescens and Uncaria.
2. Cell proliferation inhibition test:Using the tetrazolium blue (MTT) to study the antitumor activities of five effect sites-total alkaloids and the natural active ingredients on human gastric cancer cells BGC-823, MKN-45 in vitro. Survival rate= (experimental group calculated OD)/(control group OD)×100%, Inhibition rate= (1-experimental OD/ control OD)×100%.
3. Morphological observation:different concentrations of Evodia total alkaloids, berberine total alkaloids, Flavescens total alkaloids, Uncaria total alkaloids and corydalis total alkaloids to treat on human gastric cancer cell line BGC-823 and MKN-45 after observed under inverted microscope Morphological changes of treated cells, and photographed.
[Results]
1. The inhibition effect of the effective part of Evodia alkaloids, berberine alkaloids, matrine alkaloids, corydalis alkaloids, Uncaria alkaloids on human gastric cancer cell line MKN-45, BGC-823 were obviously observed and with the increase in drug concentration, inhibition rate increased in a dose dependent relationship.
2. The comparison of inhibite rate of five alkaloids between the 2μg/ml-200μg/ml human gastric cancer cell line MKN-45:Evodia alkaloids aqueous> aqueous berberine alkaloids> ethanol uncaria alkaloids> ethanol matrine alkloids> ethanol corydalis alkaloids
①Evodia alkaloids:aqueous extraction>ethanol extraction>acid extraction;
②berberine alkaloids:aquesous extraction>ethanol extraction>acid extraction;
③Flavescens alkaloids:ethanol extraction>aqueous extraction>acid extraction;
④Corydalis alkaloids:ethanol extraction>aqueous extraction>acid extraction;
⑤Uncaris alkloidst:ethanol extraction>aqueous extraction>acid extraction; The comparison of inhibition rate of five natural effective part of the active component of alkaloids in 2μg/ml-200μg/ml concetration on human gastric cancer cell line MKN-45: Aqueous extract Evodia alkaloids> rutaecarpine; aqueous berberine alkaloids> berberine; Ethanol total alkaloids
3. Five alkaloids between 6.25μg/ml-200μg/ml concentration on human gastric cancer cell line BGC-823 after 48,72 hours, with time and drug concentration, inhibition rate increased gradually in a time-dose dependent manner in a certain dose range.
4. Evodia alkaloids from aqueous extraction, Berberine alkaloids from aqueous extraction, Alkaloids ethanol, ethanol total alkaloids, Uncaria alkaloids in the role of ethanol on gastric cancer BGC-823 cells 48 hours, cell growth was inhibited, and the aqueous berberine alkaloids of IC50=20.34μg/ml, different drug concentrations were significant differences between
5. Morphologic changes:under normal circumstances, human gastric cancer cell line BGC-823 and MKN-45 were polygonal, spindle, adhered to the wall. The role of alkaloids in five, the cells became round and shrunken, reduce the number of adherent cells, cell swelling, the size of inconsistency, the cell gap widened.
[Conclusion]
1. Evodia alkaloids, berberine alkaloids, Flavescens alkaloids, Uncaria alkaloids, corydalis alkaloids in vitro have a strong inhibition of proliferation on human gastric cancer cell line BGC-823 and MKN-45 in vitro, and with the dose increased the inhibiton increased. Evodia alkaloids from aqueous extraction and berberine alkaloids from aqueous extraction have a stronger inhibitory effect on gastric cancer cells.
2. Evodia alkaloids from aqueous extraction, Berberine alkaloids from aqueous extraction, Flavescens alkaloids from ethanol extraction, Corydalis alkaloids from ethanol extraction, and Uncaria alkloids from ethanol extraction on human gastric cancer cells BGC-823 inhibition, IC50:25.76μg/30.34μg/ml、68.51μg/ml、34.50μg/ml、33.10μg/ml.
3. The inhibition the proliferation of aqueous extraction Evodia alkaloids and berberine alkaloids than the corresponding active ingredients.
引文
[1]Feigier P, Vanboof A, Sebban C, et al. Long-term results of the R-chop study in the treatment of elderly patients with diffuse large B-cell lymphoma [J]. J Clin Oncol,2005,23 (18):4117-4126.
[2]Burstein HJ, Harris LN, Gelman R,et al. Properative therapy with trastuzamab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER-2 overexpressing stage Ⅱ or Ⅲ brest cancer a pilot study [J]. J Clin Oncol,2003,21:46-53.
[3]Bensona B, Catalanop J, Meropoln J, et al. Bevacizumab (antiVEGF) plus FOLFOX4 in provious treated advanced colorectal cancer interim toxicity analysis of Eastern Cooperative Oncology Group(ECOG) study E3200 [J]. Prog Proc Am Soc Clin Oncol,2003,22:243-248.
[4]Talpaz M, Shab N, Kantajian H, et al. Dasatinib imatinib-resistant Philadelphia chromsome-positive leukemias [J]. N Engl J Med,2006,10:107-109.
[5]蔡卫民.药物基因组学在抗肿瘤药物个体化用药的应用前景[J].中国医院药学杂志,2009,29(16)：1393-1396.
[6]Marsh S, Kwok P, McLeod HL SNP databases and pharmaco genetics:great start, but a long way to go[J]. Human Mutat,2002,20:174-179.
[7]Khan J, Wei JS, Ringner M, et al. Classification and diagnostic prediction of cancers using gene expres-sion profiling and artificial neural networks[J]. Nat Med,2001,7 (6):673-679.
[8]林健,卜一珊.分子抗癌靶向药物的研究进展[J].天津药学,2005,17(2)：60-62.
[9]Zhu CQ, da Cunha Santos G, Ding K, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21[J]. J Clin Oncol,2008,26 (26):4268-75.
[10]Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer-molecular and clinical predictors of outcome [J]. N Engl J Med.2005,353 (2):133-44.
[11]Heinemann V, Stintzing S, Kirchner T, et al. Clinical relevance of EGFR-and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR[J]. Cancer Treat Rev (2008), doi:10.1016/j.ctrv.2008.11.005.
[12]Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer [J]. J Clin Oncol,2008,26 (10):1626-34.
[13]陈振锋,彭艳,谭明雄,等.基于中药活性成分的金属基抗肿瘤药物前期研究[J].化学进展,2009,20(5)：929-933.
[14]Dai ZJ, Jie Gao J, Ji ZZ. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3[J]. Journal of Ethnopharmacology,2009,123:91-96.
[15]于晓峰,邹健,冉志华.氧化苦参碱对人胃癌细胞杀伤作用的机制[J].世界华人消化杂志,2007,15(15)：1719-1724.
[16]Jun T, Y BF, Saiwah Tsao. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review of traditional use and biomedical investigations[J]. Journal of Ethnopharmacology,2009,126:5-17.
[17]高昕,王喜军.黄酮类化合物抗肿瘤作用研究进展[J].中医药信息,2005,22(5)：33-34.
[18]朱俊东,杨家驹.大豆异黄酮抗癌作用研究进展[J].国外医学,卫生学分册,1998,25(5)：2571.
[19]黄文哲,赵小辰,王峰涛,等.异黄酮类化合物抗肿瘤细胞增殖作用[J].现代中药研究与实践,2003,17(1)：50-511.
[20]单磊,张卫东,张川.皂苷类成分抗肿瘤活性的研究进展[J].中草药,2005,36(2)：295-298.
[21]邓晶,蒋永新.人参皂苷CK抗肿瘤活性研究进展[J].现代肿瘤医学,2009,17(11)：2234-2236.
[22]吴晓忠,罗素琴,刘乐乐.中药多糖抗肿瘤作用的研究进展[J].内蒙古医学院学报,2009,31(1)：81-83.
[23]Stanley G, Harvey K, Slivova V, et al. Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-betal from prostate cancer cells [J]. Biochem Biophys Res Commun,2005,330 (1):46-52.
[24]胡海燕,张洹,黄峰,等.丹参酮ⅡA对NCI-H460肺癌细胞的增殖抑制和诱导凋亡作用[J].中药材,2005,28(4)：301-303.
[25]王磊,李庆林.苦参碱抗肿瘤作用机制研究进展[J].安徽医药,2009,13(4)：360-362.
[26]郑丽端,童强松,吴翠环.姜黄素诱导人卵巢癌细胞株A278O凋亡及其分子机制的研究[J].癌症,2002,21(12)：1296-1300.
[27]黎丹戎,侯新华,张玮,等.汉黄芩素诱导人卵巢癌细胞A278O凋亡及对细胞端粒酶活性的影响[J].癌症,2003,22(8)：801-805.
[28]李贵海,刘明霞,孙付军,等.粉防己碱对获得性多药耐药小鼠S180肿瘤细胞P170LRP,TOPOⅡ表达的调控[J].中国中药杂志,2005,30(16)：1280-1282.
[29]张慧珠,杨林,刘叔梅,等.中药活性成分体外逆转肿瘤细胞多药耐药的研究[J].中药材,2001,24(9)：655-657.
[30]周于禄,唐铭翔,刘世坤.异钩藤碱对人肺腺癌细胞A549/DDP多药耐药的逆转作用.[J].中国新药杂志,2009,18(14)：1338-1342.
[31]Wang TT, Wei J, Qian XP, et al. Gambogic acid, a potent inhibitor of survivin, reverses docetaxel resistance in gastric cancer cells[J]. Cancer Letters,2008,262:214-222.
[32]李玲,胡汛,潘锵荣,等.五味子乙素对MRP介导的肿瘤多药耐药逆转作用的研究[J].同济大学报(医学版),2006,27(6)：19-22.
[33]吕秀娟,王琴,吕圭源.抗肿瘤中药的研究进展[J].中国现代中药,2006,8(5)：34-35.
[34]Lee DY, Yasuda M, Yamamoto T, et al. Bufalin inhibits endothelial cell proliferation and angiogenesis in vitro [J]. Life Sci,1997,60(2):127-134.
[35]Hisa T, Kimura Y, Takada K, et al. Shikonin, an ingredient of Lithospermum erythrorhizon, inhibits angiogenesis in vivo and in vitro [J]. Anticancer Res,1998,18(2A):783-790.
[36]Kobayashi S, Inaba K, Kimura I, et al. Inhibitory effects of tetrandrine on angiogenesis in adjuvant induced chronic inflammation and tube formation of vascular endothelial cells [J]. Biol Pharm Bull,1998, 21(4):346-349.
[37]Hahm ER, Gho YS, Park S, et al. Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis [J]. Biochem Biophys Res Commun,2004,321(2):337-344.
[38]Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppressesTNF-induced activation of nuclear transcrip tion factors NF-kappaB, activator protein21, and apop tosis:potential role of reactive oxygen intermediates and lip idperoxidation[J]. J Immunol,2000,164 (12):6509-6519.
[39]王笑民,王征,杨国旺,等.固本消瘤胶囊抑制小鼠Lewis肺癌生长及抗血管生成研究[J].中国实验方剂学杂志,2004,10(5)：50-52.
[40]王毅,刘碧清,胥方元,等.肠复康合剂对裸鼠移植性结肠癌血管生成的抑制作用[J].中国中西医结合消化杂志,2003,11(6)：325-327.
[41]刘琼,叶秀峰.中药抗血管生成机制研究进展[J].医学综述,2008,14(3)：2044-2047.
[42]梁英,韩鲁佳.黄酮类化合物药理学作用研究进展[J].中国农业大学学报,2003,8(6)：9.
[43]Nakahata N, Tsuchiya C, Nakatani K. Baicalein inhibits Raf-1-mediated phosphorylation of MEK-1 in C6 rat glioma cells.[J]. European Journal of Pharmacology,2003,46(1):1.
[44]钟芳,罗少军,汤少明.白藜芦醇抑制细胞增殖研究新进展[J].中草药,2003,34(5)：2-4.
[45]Tong kong A N, Yu R, Hebbar V, et al. Signal transduction events elicited by cancer prevention compounds [J]. Mutat Res,2001,481:231-241.
[46]李勇,刘冀红,赵群.大蒜素对人胃腺癌BGC-823细胞影响的研究[J].中国中西医结合外科杂志,2001,7(5)：307.
[47]杜鹃.中药抗肿瘤免疫的研究进展[J].中医药临床杂志,2004,16(5)：507-508.
[48]Shanb E, Yoshida Y, Sugiura T, et al. Stimulating activityof Chinesemedicinal herbs on human lymphocy tes in vitro[J]. Inte J Immunopharma,1999,21(3):149-59.
[49]解庆东.黄芪抗肿瘤机制研究与临床应用[J].医药导报,2003,2(2)：109.
[50]齐元富.人参养荣汤的研究进展.[J].国外医学·中医中药分册,1999,1(2)：18.
[51]张绪慧,陈达理,罗荣城.鳖甲煎丸对荷瘤小鼠抑瘤作用及其对胸腺、脾指数影响的实验研究[J].江苏中医药,2006,27(9)：72.
[52]周锋,秦健,朱建中,等.莲必治注射液(穿心莲内酯)免疫功能的调节作用[J].南京医科大学学报,2004,18(1)：40.
[53]刘珂.现代中药研发的回顾和思考[J].中国天然药物,2007,5(2)：87-91.
[54]蒙其淼,梁洁,吴桂凡.生物碱类化合物药理作用研究进展[J].时珍国医国药,2003,14(11)：700-702.
[55]Dai Zhi-Jun, Gao Jie, Ji Zong-Zeng, et al. Matrine induces apoptosis in gastric carcinoma cells via alternation of Fas/FasL and activation of caspase-3[J]. Journal of Ethnopharmacology,2009 (123):91-96.
[56]Luo Cong, Zhu Yong-liang, Jiang Tie-jun, et al. Matrine induced gastric cancer MKN45 cells apoptos-is via increasing pro-apoptotic molecules of Bcl-2 family[J]. Toxicology,2007 (229):245-252.
[57]殷飞,赵军艳,姚树坤,等.苦参碱对SMMC-7721细胞MAPK、JAK-STAT信号通路的影响[J].肿瘤防治研究,2008,35(2)：84-7.
[58]Bringold Frank,Serrano Manuel. Tumor suppressors and oncogenes in cellular senescence[J]. Exp Gerontol,2000,35(3):317.
[59]钟声,徐永健,张珍祥.苦参碱对肺腺癌A549细胞CC10mRNA表达的影响[J].实用医学杂志,2006,22(10)：1103-5.
[60]何松,左国庆,张燕.苦参碱对肝癌细胞HepG2端粒酶活性调控的体外研究[J].重庆医学,2008,37(3)：291-295.
[61]马凌娣,文世宏,张彦,等.苦参碱对H22荷瘤小鼠的抑瘤作用及对免疫功能的影响[J].中草药,2004,35(12)：1374-7.
[62]Jun Tang, Yibin Fenga, Saiwah Tsaoc, et al. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review of traditional use and biomedical investigations[J]. Journal of Ethnopharmacology,2009,126: 5-17.
[63]Mantena SK, Sharma SD, Katiyar SK.. Berberine, a natural product, induces Gl-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells [J]. MolCancer Ther,2006,5 (2): 296-308.
[64]Mantena SK, Som DS, Santosh KK, Berberine inhibits growth, induces G1 arrest and apoptosis in hum man epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochon drial membrane potential and cleavage of caspase 3 and PARP [J]. Carcinogenesis,2006,27:2018-2027.
[65]刘新迎,周联,王培训.小檗碱抗肿瘤机制研究进展[J].中医药学刊,2006,24(8)：1499-1501.
[66]Eom KS, Hong JM, Youn MJ, et al. Berberine induces G1 arrest and apoptosis in human gliobla stoma T98G cells through mitochondrial/caspases pathway [J]. Biological & Pharmaceutical Bulletin,2008,31: 558-562.
[67]Hsu WH, Hsieh YS, Kuo HC, et al. Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL[J]. Archives of Toxicology,2007,81:719-728.
[68]Lin S, Tsai SC, Lee CC, et al. Berberine inhibits H IF-1 alpha expression via enhanced proteolysis [J]. Mol Pharmacol,2004,66 (3):612-619.
[69]Peng PL, Hsieh YS, Wang C J, et al. Chou FP inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrixmetallo proteinase-2[J]. Toxicol Appl Pharmacol,2006,214(1):8-15.
[70]Yount G, Qian Y, Moore D, et al. Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro[J]. J Exp Ther Oncol,2004,4(2):137-143.
[71]朱丽红,刘小东,谭宇蕙,等.吴茱萸碱对人肝癌细胞HepG2的生长抑制及诱导凋亡作用[J].中国药理学通报,2009,25(1)：68-71.
[72]于彭,王楚盈,魏中元,等.吴茱萸碱抗肿瘤作用[J].吉林中医药,2008,28(3)：233.
[73]Kuo PL, Lin CC. Tetrandrine-induced cell cycle arrest and apoptosis in HepG2 cells[J]. Life Sci,2003, 73(2):243.
[74]Liu BL, Wang TT, Qian XP, et al. Anticancer effect of tetrandrine on primary cancer cell isolated from ascites and pleural fluids[J]. Cancer Letters,2008,268:166-175.
[75]Wei J, Liu BL, Wang Lf, et al. Synergistic interaction between tetrandrine and chemotherapeutic agents and in Xuence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines[J]. Can cer Chemother Pharmacol,2007,60:703-711.
[76]Fu LW, Deng ZA, FanW. Screening and discovery of novel MDR modifiers from naturally occurring bisbenzy lisoquinoline alkaloids[J]. Anticancer Res,2001,21 (4A):2273.
[77]Fu LW, Zhang YM, Liang YJ. Multidrug resistance of tumor cells was reversed by tetrandrine in vitro and in xenograft derived from human breast cancer MCF-7/adr cells [J]. Eur. J. Cancer,2002,38(3):418.
[78]刘广遐,王婷婷,魏嘉,等.4种中药提取物对多西紫杉醇耐药胃癌细胞的作用[J].江苏中医药,2008,40(4)：64-66.
[79]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠细胞膜流动性和膜蛋白水平的影响[J].中草药,2005,36(2)：239-241.
[80]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠肿瘤细胞膜唾液酸和封闭度的影响[J].中草药,2005,36(1)：79-81.
[81]季宇彬,王宏亮,高世勇.龙葵碱对肿瘤细胞膜ATP酶活性的影响[J].哈尔滨商业大学学报(自然科学版),2005,21(2)：127-129.
[82]湛学军,徐燕萍,谢大泽,等.发光法分析莪术油等中药对肝、胃癌细胞增殖活性抑制作用的实验研究[J].中国肿瘤临床,2007,34(1)：30-33.
[83]季宇彬,王宏亮,高世勇.龙葵碱对荷瘤小鼠肿瘤细胞DNA和RNA的影响[J].中草药,2005,36(8)：1200-1202.
[84]Gao S Y, W ang Q J, J i Y B. Effect of solanine on the membrane potential of mitochondria in HepG2 cells and [Ca2+] in the cells [J]. World J Gastroenterol,2006,12(21):33592-33671.
[85]高世勇,季宇彬.龙葵碱对人肝癌HepG2细胞N-乙酰基转移酶活性的影响[J].中草药,2008,39(11)：1688-1691.
[86]高世勇,季宇彬.龙葵碱诱导HepG2细胞凋亡的线粒体通路研究[J].中国药学杂志,2008,43(4)：272-275.
[87]张国铎,谢丽,禹立霞.延胡索总碱对6种人源胃癌细胞株的体外增殖抑制作用[J].中国中西医结合消化杂志,2009,17(2)：81-85.
[88]张国铎,谢丽,胡文静,等.延胡索总碱对人肝癌细胞系HepG2抑制作用及其对microRNA表达谱的影响[J].南京中医药大学学报,2009,25(7)：181-183.
[89]黄晓春,周燕虹,杨录军,等.昆明山海棠总生物碱体外抗肿瘤作用的研究[J].中国医院药学杂志, 2006,26(4)：442-445.、
[90]刘乐斌,刘胜学,胡孝贞,等.昆明山海棠总生物碱诱导肺腺癌A549细胞凋亡与细胞周期改变[J].第三军医大学学报,2007,29(1)：18-20.
[91]黄晓春,刘晋祎,周燕虹,等.昆明山海棠总生物碱对人结肠癌HCT116细胞增殖和凋亡的影响[J]第三军医大学学报,2009,31(22)：2246-2248.
[92]黄鸣清,蒋东旭,罗明俐,等.昆明山海棠抗肿瘤活性部位筛选研究[J].中国中药杂志,2009,34(20)：2633-2636.
[1]徐小龙,刘燕燕,罗平.生物碱的提取与分离纯化技术[J].江西科学,2009,27(3)：472-475.
[2]黄阁,李发美.苦地丁中生物碱的分离和结构鉴定[J].中草药,2003,34(10)：882-883.
[3]黄慧莲,刘贤旺,罗光明.吴茱萸研究进展[J].现代中药研究与实践,2003,17(3)：62-64.
[4]于澎,王楚盈,魏中元.吴茱萸碱抗肿瘤作用研究[J].吉林中医药,2008,28(3)：223.
[5]朱丽红,刘小东,谭宇蕙.吴茱萸碱对人肝癌细胞HepG2的生长抑制及诱导凋亡作用[J].中国药理学通报,2009,25(1)：68-71.
[6]Jun Tang, Yibin Feng, Saiwah Tsao. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review oftraditional use and biomedical investigations [J]. Journal of Ethnopharmacology,2009,126:5-17.
[7]王盟,刘卫.钩藤总生物碱的研究进展[J].实用医药杂志,2008,25(3)：360-362.
[8]周于禄,唐铭翔,刘世坤.异钩藤碱对人肺腺癌细胞A549/DDP多药耐药的逆转作用[J].中国新药杂志,2009,18(14)：1338-1342.
[9]张国铎,谢丽,禹立霞.延胡索总碱对6种人源胃癌细胞株的体外增殖抑制作用[J].中国中西医结合消化杂志,2009,17(2)：81-85.
[10]杨秀伟,冉福香,王瑞卿,等.44种生物碱类化合物对人胃癌细胞株BGC和人肝癌细胞株BEL-7402细胞增殖抑制活性的筛选[J].中国现代中药,2007,9(2)：6-9.
[11]张晓丽,曹国宪,俞惠新.延胡索乙素逆转多药耐药性人乳腺癌细胞MCF-7延胡索乙素逆转多药耐药性人乳腺癌细胞MCF-7[J].中药药理与临床,2005,21(6)：19-21.
[12]王磊,李庆林.苦参碱抗肿瘤作用机制研究进展[J].安徽医药,2009,13(4)：360-364.
[13]于晓峰,邹健,冉志华.氧化苦参碱对人胃癌细胞杀伤作用的机制[J].世界华人消化杂志2007,15(15)：1719-1724.
[14]李雅臣,马雪梅,陈鸿英.钩藤总生物碱提取溶剂的选择探讨[J].天津中医药,2003,20(4)：67.
[1]贾敏如.防治恶性肿瘤的天然药物[J].成都中医药大学学报,2002,25(2)：25-31.
[2]李振涛,朱奇,纪宇.植物生物碱抗肿瘤作用机制的研究进展[J].药学进展,2005,29(5)：193-196
[3]杨秀伟,冉福香,王瑞卿44种生物碱类化合物对人胃癌细胞株BGC和人肝癌细胞株BEL-7402细胞增殖抑制活性的筛选[J].中国现代中药,2007,119(12)：6-9.
[4]宋宇,宋颖,康治臣.吴茱萸碱体外抗肿瘤作用[J].中国临床药理学与治疗学,2008,13(8)：860-864.
[5]宋颖,赵文杰,宋宇.吴茱萸碱体内抗肿瘤作用的研究[J].吉林中医药,2008,28(12)：934-935
[6]程磊,周秀佳.植物生物碱抗肿瘤机制[J].中草药,2004,35(2)：216-220.
[7]王明军.试论现代中药衍生的“有效部位配伍”新药模式[J].中国中西医结合杂志,2008,28(1)：73-76.
[8]冯秀章.重视中药二类新药有效部位研究,提高中药新药研制水平[J].中国新药与临床药理,1998,9(3)：134-137.
[1]Dai Zhi-Jun, Gao Jie, Ji Zong-Zeng, et al. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3[J]. Journal of Ethnopharmacology,2009 (123):91-96.
[2]Luo Cong, Zhu Yong-liang, Jiang Tie-jun, et al. Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family[J]. Toxicology,2007 (229):245-252.
[3]殷飞,赵军艳,姚树坤,等.苦参碱对SMMC-7721细胞MAPK、JAK-STAT信号通路的影响[J].肿瘤防治研究,2008,35(2)：84-7.
[4]Bringold Frank,Serrano Manuel. Tumor suppressors and oncogenes in cellular senescence[J]. Exp Gerontol,2000,35(3):317.
[5]钟声,徐永健,张珍祥.苦参碱对肺腺癌A549细胞CC10mRNA表达的影响[J].实用医学杂志,2006,22(10)：1103-5.
[6]何松,左国庆,张燕.苦参碱对肝癌细胞HepG2端粒酶活性调控的体外研究[J].重庆医学,2008,37(3)：291-295.
[7]马凌娣,文世宏,张彦,等.苦参碱对H22荷瘤小鼠的抑瘤作用及对免疫功能的影响[J].中草药,2004,35(12)：1374-7.
[8]Jun Tang, Yibin Fenga,, Saiwah Tsaoc,et al. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review of traditional use and biomedical investigations [J]. Journal of Ethnopharmacology,2009,126: 5-17.
[9]Mantena SK, Sharma SD, Katiyar SK. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells [J]. MolCancer Ther,2006,5(2):296-308.
[10]Mantena SK, Som DS, Santosh KK, Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP [J]. Carcinogenesis,2006,27:2018-2027.
[11]刘新迎,周联,王培训.小檗碱抗肿瘤机制研究进展[J].中医药学刊,2006,24(8)：1499-1501.
[12]Eom KS, Hong JM, Youn MJ, et al. Berberine induces G1 arrest and apoptosis in human gliobla stoma T98G cells through mitochondrial/caspases pathway[J]. Biological & Pharmaceutical Bulletin,2008,31, 558-562.
[13]Hsu WH, Hsieh YS, Kuo HC, et al. Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL[J]. Archives of Toxicology,2007,81:719-728.
[14]Lin S, Tsai SC, Lee CC, et al. Berberine inhibits H IF-1 alpha expression via enhanced proteolysis [J]. Mol Pharmacol,2004,66 (3):612-619.
[15]Peng PL, Hsieh YS, Wang C J, et al. Chou FP inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrixmetallo proteinase-2 [J]. Toxicol Appl Pharmacol,2006,214(1):8-15.
[16]Yount G, Qian Y, Moore D, et al. Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro[J]. J Exp Ther Oncol,2004,4 (2):137-143.
[17]朱丽红,刘小东,谭宇蕙,等.吴茱萸碱对人肝癌细胞HepG2的生长抑制及诱导凋亡作用[J].中国药理学通报,2009,25(1)：68-71.
[18]于彭,王楚盈,魏中元,等.吴茱萸碱抗肿瘤作用[J].吉林中医药,2008,28(3)：233.
[19]Kuo PL, Lin CC. Tetrandrine-induced cell cycle arrest and apoptosis in HepG2 cells[J]. Life Sci,2003, 73(2):243.
[20]Liu BL, Wang TT, Qian XP, et al. Anticancer effect of tetrandrine on primary cancer cell isolated from ascites and pleural fluids[J]. Cancer Letters,2008,268:166-175.
[21]Wei J, Liu BL, Wang Lf, et al. Synergistic interaction between tetrandrine and chemotherapeutic agents and inXuence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines[J]. Cancer Chemother Pharmacol,2007,60:703-711.
[22]Fu LW, Deng ZA, FanW. Screening and discovery of novelMDR modifiers from naturally occurring bisbenzy lisoquinoline alkaloids[J]. Anticancer Res,2001,21 (4A):2273.
[23]Fu LW, Zhang YM, Liang YJ. Multidrug resistance of tumor cells was reversed by tetrandrine in vitro and in xenograft derived from human breast cancer MCF-7/adr cells [J]. Eur. J. Cancer,2002,38(3):418.
[24]刘广遐,王婷婷,魏嘉,等.4种中药提取物对多西紫杉醇耐药胃癌细胞的作用[J].江苏中医药,2008,40(4)：64-66.
[25]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠细胞膜流动性和膜蛋白水平的影响[J].中草药,2005,36(2)：239-241.
[26]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠肿瘤细胞膜唾液酸和封闭度的影响[J].中草药,2005,36(1)：79-81.
[27]季宇彬,王宏亮,高世勇.龙葵碱对肿瘤细胞膜ATP酶活性的影响[J].哈尔滨商业大学学报(自然科学版),2005,21(2)：127-129.
[28]湛学军,徐燕萍,谢大泽,等.发光法分析莪术油等中药对肝、胃癌细胞增殖活性抑制作用的实验研究[J].中国肿瘤临床,2007,34(1)：30-33.
[29]季宇彬,王宏亮,高世勇.龙葵碱对荷瘤小鼠肿瘤细胞DNA和RNA的影响[J].中草药,2005,36(8)：1200-1202.
[30]Gao S Y, W ang Q J,Ji Y B. Effect of solanine on the membrane potential of mitochondria in HepG2 cells and [Ca2+] in the cells [J]. World J Gastroenterol,2006,12 (21):33592-33671.
[31]高世勇,季宇彬.龙葵碱对人肝癌HepG2细胞N-乙酰基转移酶活性的影响[J].中草药,2008,39(11)：1688-1691.
[32]高世勇,季宇彬.龙葵碱诱导HepG2细胞凋亡的线粒体通路研究[J].中国药学杂志,2008,43(4)：272-275.
[33]张国铎,谢丽,禹立霞.延胡索总碱对6种人源胃癌细胞株的体外增殖抑制作用[J].中国中西医结合消化杂志,2009,17(2)：81-85.
[34]张国铎,谢丽,胡文静,等.延胡索总碱对人肝癌细胞系HepG2抑制作用及其对microRNA表达的影响[J].南京中医药大学学报,2009,25(7)：181-183.
[35]黄晓春,周燕虹,杨录军,等.昆明山海棠总生物碱体外抗肿瘤作用的研究[J].中国医院药学杂志,2006,26(4)：442445.
[36]刘乐斌,刘胜学,胡孝贞,等.昆明山海棠总生物碱诱导肺腺癌A549细胞凋亡与细胞周期改变[J].第三军医大学学报,2007,29(1)：18-20.
[37]黄晓春,刘晋祎,周燕虹,等.昆明山海棠总生物碱对人结肠癌HCT1 16细胞增殖和凋亡的影响[J]第三军医大学学报,2009,31(22)：2246-2248.
[38]黄鸣清,蒋东旭,罗明俐,等.昆明山海棠抗肿瘤活性部位筛选研究[J].中国中药杂志,2009,34(20)：2633-2636.
[2]Burstein HJ, Harris LN, Gelman R,et al. Properative therapy with trastuzamab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER-2 overexpressing stage Ⅱ or Ⅲ brest cancer a pilot study [J]. J Clin Oncol,2003,21:46-53.
[3]Bensona B, Catalanop J, Meropoln J, et al. Bevacizumab (antiVEGF) plus FOLFOX4 in provious treated advanced colorectal cancer interim toxicity analysis of Eastern Cooperative Oncology Group(ECOG) study E3200 [J]. Prog Proc Am Soc Clin Oncol,2003,22:243-248.
[4]Talpaz M, Shab N, Kantajian H, et al. Dasatinib imatinib-resistant Philadelphia chromsome-positive leukemias [J]. N Engl J Med,2006,10:107-109.
[5]蔡卫民.药物基因组学在抗肿瘤药物个体化用药的应用前景[J].中国医院药学杂志,2009,29(16)：1393-1396.
[6]Marsh S, Kwok P, McLeod HL SNP databases and pharmaco genetics:great start, but a long way to go[J]. Human Mutat,2002,20:174-179.
[7]Khan J, Wei JS, Ringner M, et al. Classification and diagnostic prediction of cancers using gene expres-sion profiling and artificial neural networks[J]. Nat Med,2001,7 (6):673-679.
[8]林健,卜一珊.分子抗癌靶向药物的研究进展[J].天津药学,2005,17(2)：60-62.
[9]Zhu CQ, da Cunha Santos G, Ding K, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21[J]. J Clin Oncol,2008,26 (26):4268-75.
[10]Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer-molecular and clinical predictors of outcome [J]. N Engl J Med.2005,353 (2):133-44.
[11]Heinemann V, Stintzing S, Kirchner T, et al. Clinical relevance of EGFR-and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR[J]. Cancer Treat Rev (2008), doi:10.1016/j.ctrv.2008.11.005.
[12]Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer [J]. J Clin Oncol,2008,26 (10):1626-34.
[13]陈振锋,彭艳,谭明雄,等.基于中药活性成分的金属基抗肿瘤药物前期研究[J].化学进展,2009,20(5)：929-933.
[14]Dai ZJ, Jie Gao J, Ji ZZ. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3[J]. Journal of Ethnopharmacology,2009,123:91-96.
[15]于晓峰,邹健,冉志华.氧化苦参碱对人胃癌细胞杀伤作用的机制[J].世界华人消化杂志,2007,15(15)：1719-1724.
[16]Jun T, Y BF, Saiwah Tsao. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review of traditional use and biomedical investigations[J]. Journal of Ethnopharmacology,2009,126:5-17.
[17]高昕,王喜军.黄酮类化合物抗肿瘤作用研究进展[J].中医药信息,2005,22(5)：33-34.
[18]朱俊东,杨家驹.大豆异黄酮抗癌作用研究进展[J].国外医学,卫生学分册,1998,25(5)：2571.
[19]黄文哲,赵小辰,王峰涛,等.异黄酮类化合物抗肿瘤细胞增殖作用[J].现代中药研究与实践,2003,17(1)：50-511.
[20]单磊,张卫东,张川.皂苷类成分抗肿瘤活性的研究进展[J].中草药,2005,36(2)：295-298.
[21]邓晶,蒋永新.人参皂苷CK抗肿瘤活性研究进展[J].现代肿瘤医学,2009,17(11)：2234-2236.
[22]吴晓忠,罗素琴,刘乐乐.中药多糖抗肿瘤作用的研究进展[J].内蒙古医学院学报,2009,31(1)：81-83.
[23]Stanley G, Harvey K, Slivova V, et al. Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-betal from prostate cancer cells [J]. Biochem Biophys Res Commun,2005,330 (1):46-52.
[24]胡海燕,张洹,黄峰,等.丹参酮ⅡA对NCI-H460肺癌细胞的增殖抑制和诱导凋亡作用[J].中药材,2005,28(4)：301-303.
[25]王磊,李庆林.苦参碱抗肿瘤作用机制研究进展[J].安徽医药,2009,13(4)：360-362.
[26]郑丽端,童强松,吴翠环.姜黄素诱导人卵巢癌细胞株A278O凋亡及其分子机制的研究[J].癌症,2002,21(12)：1296-1300.
[27]黎丹戎,侯新华,张玮,等.汉黄芩素诱导人卵巢癌细胞A278O凋亡及对细胞端粒酶活性的影响[J].癌症,2003,22(8)：801-805.
[28]李贵海,刘明霞,孙付军,等.粉防己碱对获得性多药耐药小鼠S180肿瘤细胞P170LRP,TOPOⅡ表达的调控[J].中国中药杂志,2005,30(16)：1280-1282.
[29]张慧珠,杨林,刘叔梅,等.中药活性成分体外逆转肿瘤细胞多药耐药的研究[J].中药材,2001,24(9)：655-657.
[30]周于禄,唐铭翔,刘世坤.异钩藤碱对人肺腺癌细胞A549/DDP多药耐药的逆转作用.[J].中国新药杂志,2009,18(14)：1338-1342.
[31]Wang TT, Wei J, Qian XP, et al. Gambogic acid, a potent inhibitor of survivin, reverses docetaxel resistance in gastric cancer cells[J]. Cancer Letters,2008,262:214-222.
[32]李玲,胡汛,潘锵荣,等.五味子乙素对MRP介导的肿瘤多药耐药逆转作用的研究[J].同济大学报(医学版),2006,27(6)：19-22.
[33]吕秀娟,王琴,吕圭源.抗肿瘤中药的研究进展[J].中国现代中药,2006,8(5)：34-35.
[34]Lee DY, Yasuda M, Yamamoto T, et al. Bufalin inhibits endothelial cell proliferation and angiogenesis in vitro [J]. Life Sci,1997,60(2):127-134.
[35]Hisa T, Kimura Y, Takada K, et al. Shikonin, an ingredient of Lithospermum erythrorhizon, inhibits angiogenesis in vivo and in vitro [J]. Anticancer Res,1998,18(2A):783-790.
[36]Kobayashi S, Inaba K, Kimura I, et al. Inhibitory effects of tetrandrine on angiogenesis in adjuvant induced chronic inflammation and tube formation of vascular endothelial cells [J]. Biol Pharm Bull,1998, 21(4):346-349.
[37]Hahm ER, Gho YS, Park S, et al. Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis [J]. Biochem Biophys Res Commun,2004,321(2):337-344.
[38]Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppressesTNF-induced activation of nuclear transcrip tion factors NF-kappaB, activator protein21, and apop tosis:potential role of reactive oxygen intermediates and lip idperoxidation[J]. J Immunol,2000,164 (12):6509-6519.
[39]王笑民,王征,杨国旺,等.固本消瘤胶囊抑制小鼠Lewis肺癌生长及抗血管生成研究[J].中国实验方剂学杂志,2004,10(5)：50-52.
[40]王毅,刘碧清,胥方元,等.肠复康合剂对裸鼠移植性结肠癌血管生成的抑制作用[J].中国中西医结合消化杂志,2003,11(6)：325-327.
[41]刘琼,叶秀峰.中药抗血管生成机制研究进展[J].医学综述,2008,14(3)：2044-2047.
[42]梁英,韩鲁佳.黄酮类化合物药理学作用研究进展[J].中国农业大学学报,2003,8(6)：9.
[43]Nakahata N, Tsuchiya C, Nakatani K. Baicalein inhibits Raf-1-mediated phosphorylation of MEK-1 in C6 rat glioma cells.[J]. European Journal of Pharmacology,2003,46(1):1.
[44]钟芳,罗少军,汤少明.白藜芦醇抑制细胞增殖研究新进展[J].中草药,2003,34(5)：2-4.
[45]Tong kong A N, Yu R, Hebbar V, et al. Signal transduction events elicited by cancer prevention compounds [J]. Mutat Res,2001,481:231-241.
[46]李勇,刘冀红,赵群.大蒜素对人胃腺癌BGC-823细胞影响的研究[J].中国中西医结合外科杂志,2001,7(5)：307.
[47]杜鹃.中药抗肿瘤免疫的研究进展[J].中医药临床杂志,2004,16(5)：507-508.
[48]Shanb E, Yoshida Y, Sugiura T, et al. Stimulating activityof Chinesemedicinal herbs on human lymphocy tes in vitro[J]. Inte J Immunopharma,1999,21(3):149-59.
[49]解庆东.黄芪抗肿瘤机制研究与临床应用[J].医药导报,2003,2(2)：109.
[50]齐元富.人参养荣汤的研究进展.[J].国外医学·中医中药分册,1999,1(2)：18.
[51]张绪慧,陈达理,罗荣城.鳖甲煎丸对荷瘤小鼠抑瘤作用及其对胸腺、脾指数影响的实验研究[J].江苏中医药,2006,27(9)：72.
[52]周锋,秦健,朱建中,等.莲必治注射液(穿心莲内酯)免疫功能的调节作用[J].南京医科大学学报,2004,18(1)：40.
[53]刘珂.现代中药研发的回顾和思考[J].中国天然药物,2007,5(2)：87-91.
[54]蒙其淼,梁洁,吴桂凡.生物碱类化合物药理作用研究进展[J].时珍国医国药,2003,14(11)：700-702.
[55]Dai Zhi-Jun, Gao Jie, Ji Zong-Zeng, et al. Matrine induces apoptosis in gastric carcinoma cells via alternation of Fas/FasL and activation of caspase-3[J]. Journal of Ethnopharmacology,2009 (123):91-96.
[56]Luo Cong, Zhu Yong-liang, Jiang Tie-jun, et al. Matrine induced gastric cancer MKN45 cells apoptos-is via increasing pro-apoptotic molecules of Bcl-2 family[J]. Toxicology,2007 (229):245-252.
[57]殷飞,赵军艳,姚树坤,等.苦参碱对SMMC-7721细胞MAPK、JAK-STAT信号通路的影响[J].肿瘤防治研究,2008,35(2)：84-7.
[58]Bringold Frank,Serrano Manuel. Tumor suppressors and oncogenes in cellular senescence[J]. Exp Gerontol,2000,35(3):317.
[59]钟声,徐永健,张珍祥.苦参碱对肺腺癌A549细胞CC10mRNA表达的影响[J].实用医学杂志,2006,22(10)：1103-5.
[60]何松,左国庆,张燕.苦参碱对肝癌细胞HepG2端粒酶活性调控的体外研究[J].重庆医学,2008,37(3)：291-295.
[61]马凌娣,文世宏,张彦,等.苦参碱对H22荷瘤小鼠的抑瘤作用及对免疫功能的影响[J].中草药,2004,35(12)：1374-7.
[62]Jun Tang, Yibin Fenga, Saiwah Tsaoc, et al. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review of traditional use and biomedical investigations[J]. Journal of Ethnopharmacology,2009,126: 5-17.
[63]Mantena SK, Sharma SD, Katiyar SK.. Berberine, a natural product, induces Gl-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells [J]. MolCancer Ther,2006,5 (2): 296-308.
[64]Mantena SK, Som DS, Santosh KK, Berberine inhibits growth, induces G1 arrest and apoptosis in hum man epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochon drial membrane potential and cleavage of caspase 3 and PARP [J]. Carcinogenesis,2006,27:2018-2027.
[65]刘新迎,周联,王培训.小檗碱抗肿瘤机制研究进展[J].中医药学刊,2006,24(8)：1499-1501.
[66]Eom KS, Hong JM, Youn MJ, et al. Berberine induces G1 arrest and apoptosis in human gliobla stoma T98G cells through mitochondrial/caspases pathway [J]. Biological & Pharmaceutical Bulletin,2008,31: 558-562.
[67]Hsu WH, Hsieh YS, Kuo HC, et al. Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL[J]. Archives of Toxicology,2007,81:719-728.
[68]Lin S, Tsai SC, Lee CC, et al. Berberine inhibits H IF-1 alpha expression via enhanced proteolysis [J]. Mol Pharmacol,2004,66 (3):612-619.
[69]Peng PL, Hsieh YS, Wang C J, et al. Chou FP inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrixmetallo proteinase-2[J]. Toxicol Appl Pharmacol,2006,214(1):8-15.
[70]Yount G, Qian Y, Moore D, et al. Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro[J]. J Exp Ther Oncol,2004,4(2):137-143.
[71]朱丽红,刘小东,谭宇蕙,等.吴茱萸碱对人肝癌细胞HepG2的生长抑制及诱导凋亡作用[J].中国药理学通报,2009,25(1)：68-71.
[72]于彭,王楚盈,魏中元,等.吴茱萸碱抗肿瘤作用[J].吉林中医药,2008,28(3)：233.
[73]Kuo PL, Lin CC. Tetrandrine-induced cell cycle arrest and apoptosis in HepG2 cells[J]. Life Sci,2003, 73(2):243.
[74]Liu BL, Wang TT, Qian XP, et al. Anticancer effect of tetrandrine on primary cancer cell isolated from ascites and pleural fluids[J]. Cancer Letters,2008,268:166-175.
[75]Wei J, Liu BL, Wang Lf, et al. Synergistic interaction between tetrandrine and chemotherapeutic agents and in Xuence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines[J]. Can cer Chemother Pharmacol,2007,60:703-711.
[76]Fu LW, Deng ZA, FanW. Screening and discovery of novel MDR modifiers from naturally occurring bisbenzy lisoquinoline alkaloids[J]. Anticancer Res,2001,21 (4A):2273.
[77]Fu LW, Zhang YM, Liang YJ. Multidrug resistance of tumor cells was reversed by tetrandrine in vitro and in xenograft derived from human breast cancer MCF-7/adr cells [J]. Eur. J. Cancer,2002,38(3):418.
[78]刘广遐,王婷婷,魏嘉,等.4种中药提取物对多西紫杉醇耐药胃癌细胞的作用[J].江苏中医药,2008,40(4)：64-66.
[79]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠细胞膜流动性和膜蛋白水平的影响[J].中草药,2005,36(2)：239-241.
[80]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠肿瘤细胞膜唾液酸和封闭度的影响[J].中草药,2005,36(1)：79-81.
[81]季宇彬,王宏亮,高世勇.龙葵碱对肿瘤细胞膜ATP酶活性的影响[J].哈尔滨商业大学学报(自然科学版),2005,21(2)：127-129.
[82]湛学军,徐燕萍,谢大泽,等.发光法分析莪术油等中药对肝、胃癌细胞增殖活性抑制作用的实验研究[J].中国肿瘤临床,2007,34(1)：30-33.
[83]季宇彬,王宏亮,高世勇.龙葵碱对荷瘤小鼠肿瘤细胞DNA和RNA的影响[J].中草药,2005,36(8)：1200-1202.
[84]Gao S Y, W ang Q J, J i Y B. Effect of solanine on the membrane potential of mitochondria in HepG2 cells and [Ca2+] in the cells [J]. World J Gastroenterol,2006,12(21):33592-33671.
[85]高世勇,季宇彬.龙葵碱对人肝癌HepG2细胞N-乙酰基转移酶活性的影响[J].中草药,2008,39(11)：1688-1691.
[86]高世勇,季宇彬.龙葵碱诱导HepG2细胞凋亡的线粒体通路研究[J].中国药学杂志,2008,43(4)：272-275.
[87]张国铎,谢丽,禹立霞.延胡索总碱对6种人源胃癌细胞株的体外增殖抑制作用[J].中国中西医结合消化杂志,2009,17(2)：81-85.
[88]张国铎,谢丽,胡文静,等.延胡索总碱对人肝癌细胞系HepG2抑制作用及其对microRNA表达谱的影响[J].南京中医药大学学报,2009,25(7)：181-183.
[89]黄晓春,周燕虹,杨录军,等.昆明山海棠总生物碱体外抗肿瘤作用的研究[J].中国医院药学杂志, 2006,26(4)：442-445.、
[90]刘乐斌,刘胜学,胡孝贞,等.昆明山海棠总生物碱诱导肺腺癌A549细胞凋亡与细胞周期改变[J].第三军医大学学报,2007,29(1)：18-20.
[91]黄晓春,刘晋祎,周燕虹,等.昆明山海棠总生物碱对人结肠癌HCT116细胞增殖和凋亡的影响[J]第三军医大学学报,2009,31(22)：2246-2248.
[92]黄鸣清,蒋东旭,罗明俐,等.昆明山海棠抗肿瘤活性部位筛选研究[J].中国中药杂志,2009,34(20)：2633-2636.
[1]徐小龙,刘燕燕,罗平.生物碱的提取与分离纯化技术[J].江西科学,2009,27(3)：472-475.
[2]黄阁,李发美.苦地丁中生物碱的分离和结构鉴定[J].中草药,2003,34(10)：882-883.
[3]黄慧莲,刘贤旺,罗光明.吴茱萸研究进展[J].现代中药研究与实践,2003,17(3)：62-64.
[4]于澎,王楚盈,魏中元.吴茱萸碱抗肿瘤作用研究[J].吉林中医药,2008,28(3)：223.
[5]朱丽红,刘小东,谭宇蕙.吴茱萸碱对人肝癌细胞HepG2的生长抑制及诱导凋亡作用[J].中国药理学通报,2009,25(1)：68-71.
[6]Jun Tang, Yibin Feng, Saiwah Tsao. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review oftraditional use and biomedical investigations [J]. Journal of Ethnopharmacology,2009,126:5-17.
[7]王盟,刘卫.钩藤总生物碱的研究进展[J].实用医药杂志,2008,25(3)：360-362.
[8]周于禄,唐铭翔,刘世坤.异钩藤碱对人肺腺癌细胞A549/DDP多药耐药的逆转作用[J].中国新药杂志,2009,18(14)：1338-1342.
[9]张国铎,谢丽,禹立霞.延胡索总碱对6种人源胃癌细胞株的体外增殖抑制作用[J].中国中西医结合消化杂志,2009,17(2)：81-85.
[10]杨秀伟,冉福香,王瑞卿,等.44种生物碱类化合物对人胃癌细胞株BGC和人肝癌细胞株BEL-7402细胞增殖抑制活性的筛选[J].中国现代中药,2007,9(2)：6-9.
[11]张晓丽,曹国宪,俞惠新.延胡索乙素逆转多药耐药性人乳腺癌细胞MCF-7延胡索乙素逆转多药耐药性人乳腺癌细胞MCF-7[J].中药药理与临床,2005,21(6)：19-21.
[12]王磊,李庆林.苦参碱抗肿瘤作用机制研究进展[J].安徽医药,2009,13(4)：360-364.
[13]于晓峰,邹健,冉志华.氧化苦参碱对人胃癌细胞杀伤作用的机制[J].世界华人消化杂志2007,15(15)：1719-1724.
[14]李雅臣,马雪梅,陈鸿英.钩藤总生物碱提取溶剂的选择探讨[J].天津中医药,2003,20(4)：67.
[1]贾敏如.防治恶性肿瘤的天然药物[J].成都中医药大学学报,2002,25(2)：25-31.
[2]李振涛,朱奇,纪宇.植物生物碱抗肿瘤作用机制的研究进展[J].药学进展,2005,29(5)：193-196
[3]杨秀伟,冉福香,王瑞卿44种生物碱类化合物对人胃癌细胞株BGC和人肝癌细胞株BEL-7402细胞增殖抑制活性的筛选[J].中国现代中药,2007,119(12)：6-9.
[4]宋宇,宋颖,康治臣.吴茱萸碱体外抗肿瘤作用[J].中国临床药理学与治疗学,2008,13(8)：860-864.
[5]宋颖,赵文杰,宋宇.吴茱萸碱体内抗肿瘤作用的研究[J].吉林中医药,2008,28(12)：934-935
[6]程磊,周秀佳.植物生物碱抗肿瘤机制[J].中草药,2004,35(2)：216-220.
[7]王明军.试论现代中药衍生的“有效部位配伍”新药模式[J].中国中西医结合杂志,2008,28(1)：73-76.
[8]冯秀章.重视中药二类新药有效部位研究,提高中药新药研制水平[J].中国新药与临床药理,1998,9(3)：134-137.
[1]Dai Zhi-Jun, Gao Jie, Ji Zong-Zeng, et al. Matrine induces apoptosis in gastric carcinoma cells via alteration of Fas/FasL and activation of caspase-3[J]. Journal of Ethnopharmacology,2009 (123):91-96.
[2]Luo Cong, Zhu Yong-liang, Jiang Tie-jun, et al. Matrine induced gastric cancer MKN45 cells apoptosis via increasing pro-apoptotic molecules of Bcl-2 family[J]. Toxicology,2007 (229):245-252.
[3]殷飞,赵军艳,姚树坤,等.苦参碱对SMMC-7721细胞MAPK、JAK-STAT信号通路的影响[J].肿瘤防治研究,2008,35(2)：84-7.
[4]Bringold Frank,Serrano Manuel. Tumor suppressors and oncogenes in cellular senescence[J]. Exp Gerontol,2000,35(3):317.
[5]钟声,徐永健,张珍祥.苦参碱对肺腺癌A549细胞CC10mRNA表达的影响[J].实用医学杂志,2006,22(10)：1103-5.
[6]何松,左国庆,张燕.苦参碱对肝癌细胞HepG2端粒酶活性调控的体外研究[J].重庆医学,2008,37(3)：291-295.
[7]马凌娣,文世宏,张彦,等.苦参碱对H22荷瘤小鼠的抑瘤作用及对免疫功能的影响[J].中草药,2004,35(12)：1374-7.
[8]Jun Tang, Yibin Fenga,, Saiwah Tsaoc,et al. Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review of traditional use and biomedical investigations [J]. Journal of Ethnopharmacology,2009,126: 5-17.
[9]Mantena SK, Sharma SD, Katiyar SK. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells [J]. MolCancer Ther,2006,5(2):296-308.
[10]Mantena SK, Som DS, Santosh KK, Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP [J]. Carcinogenesis,2006,27:2018-2027.
[11]刘新迎,周联,王培训.小檗碱抗肿瘤机制研究进展[J].中医药学刊,2006,24(8)：1499-1501.
[12]Eom KS, Hong JM, Youn MJ, et al. Berberine induces G1 arrest and apoptosis in human gliobla stoma T98G cells through mitochondrial/caspases pathway[J]. Biological & Pharmaceutical Bulletin,2008,31, 558-562.
[13]Hsu WH, Hsieh YS, Kuo HC, et al. Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL[J]. Archives of Toxicology,2007,81:719-728.
[14]Lin S, Tsai SC, Lee CC, et al. Berberine inhibits H IF-1 alpha expression via enhanced proteolysis [J]. Mol Pharmacol,2004,66 (3):612-619.
[15]Peng PL, Hsieh YS, Wang C J, et al. Chou FP inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrixmetallo proteinase-2 [J]. Toxicol Appl Pharmacol,2006,214(1):8-15.
[16]Yount G, Qian Y, Moore D, et al. Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro[J]. J Exp Ther Oncol,2004,4 (2):137-143.
[17]朱丽红,刘小东,谭宇蕙,等.吴茱萸碱对人肝癌细胞HepG2的生长抑制及诱导凋亡作用[J].中国药理学通报,2009,25(1)：68-71.
[18]于彭,王楚盈,魏中元,等.吴茱萸碱抗肿瘤作用[J].吉林中医药,2008,28(3)：233.
[19]Kuo PL, Lin CC. Tetrandrine-induced cell cycle arrest and apoptosis in HepG2 cells[J]. Life Sci,2003, 73(2):243.
[20]Liu BL, Wang TT, Qian XP, et al. Anticancer effect of tetrandrine on primary cancer cell isolated from ascites and pleural fluids[J]. Cancer Letters,2008,268:166-175.
[21]Wei J, Liu BL, Wang Lf, et al. Synergistic interaction between tetrandrine and chemotherapeutic agents and inXuence of tetrandrine on chemotherapeutic agent-associated genes in human gastric cancer cell lines[J]. Cancer Chemother Pharmacol,2007,60:703-711.
[22]Fu LW, Deng ZA, FanW. Screening and discovery of novelMDR modifiers from naturally occurring bisbenzy lisoquinoline alkaloids[J]. Anticancer Res,2001,21 (4A):2273.
[23]Fu LW, Zhang YM, Liang YJ. Multidrug resistance of tumor cells was reversed by tetrandrine in vitro and in xenograft derived from human breast cancer MCF-7/adr cells [J]. Eur. J. Cancer,2002,38(3):418.
[24]刘广遐,王婷婷,魏嘉,等.4种中药提取物对多西紫杉醇耐药胃癌细胞的作用[J].江苏中医药,2008,40(4)：64-66.
[25]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠细胞膜流动性和膜蛋白水平的影响[J].中草药,2005,36(2)：239-241.
[26]季宇彬,王胜惠,高世勇,等.龙葵碱对H22荷瘤小鼠肿瘤细胞膜唾液酸和封闭度的影响[J].中草药,2005,36(1)：79-81.
[27]季宇彬,王宏亮,高世勇.龙葵碱对肿瘤细胞膜ATP酶活性的影响[J].哈尔滨商业大学学报(自然科学版),2005,21(2)：127-129.
[28]湛学军,徐燕萍,谢大泽,等.发光法分析莪术油等中药对肝、胃癌细胞增殖活性抑制作用的实验研究[J].中国肿瘤临床,2007,34(1)：30-33.
[29]季宇彬,王宏亮,高世勇.龙葵碱对荷瘤小鼠肿瘤细胞DNA和RNA的影响[J].中草药,2005,36(8)：1200-1202.
[30]Gao S Y, W ang Q J,Ji Y B. Effect of solanine on the membrane potential of mitochondria in HepG2 cells and [Ca2+] in the cells [J]. World J Gastroenterol,2006,12 (21):33592-33671.
[31]高世勇,季宇彬.龙葵碱对人肝癌HepG2细胞N-乙酰基转移酶活性的影响[J].中草药,2008,39(11)：1688-1691.
[32]高世勇,季宇彬.龙葵碱诱导HepG2细胞凋亡的线粒体通路研究[J].中国药学杂志,2008,43(4)：272-275.
[33]张国铎,谢丽,禹立霞.延胡索总碱对6种人源胃癌细胞株的体外增殖抑制作用[J].中国中西医结合消化杂志,2009,17(2)：81-85.
[34]张国铎,谢丽,胡文静,等.延胡索总碱对人肝癌细胞系HepG2抑制作用及其对microRNA表达的影响[J].南京中医药大学学报,2009,25(7)：181-183.
[35]黄晓春,周燕虹,杨录军,等.昆明山海棠总生物碱体外抗肿瘤作用的研究[J].中国医院药学杂志,2006,26(4)：442445.
[36]刘乐斌,刘胜学,胡孝贞,等.昆明山海棠总生物碱诱导肺腺癌A549细胞凋亡与细胞周期改变[J].第三军医大学学报,2007,29(1)：18-20.
[37]黄晓春,刘晋祎,周燕虹,等.昆明山海棠总生物碱对人结肠癌HCT1 16细胞增殖和凋亡的影响[J]第三军医大学学报,2009,31(22)：2246-2248.
[38]黄鸣清,蒋东旭,罗明俐,等.昆明山海棠抗肿瘤活性部位筛选研究[J].中国中药杂志,2009,34(20)：2633-2636.