泽泻醇B诱导胃癌细胞凋亡、抑制其侵袭、转移的机制研究
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摘要
胃癌是我国常见的恶性肿瘤,占消化道恶性肿瘤第一位,是目前对人类健康和生命威胁最大的恶性肿瘤之一,已成为绝大多数国家因癌症死亡的首要原因。目前对胃癌的治疗还是传统的手术、化疗和放疗。尽管传统治疗方法取得了显著进展,但胃癌的病死率仍然居高不下,同时化疗和放疗也往往给患者带来较大的毒副作用。近年来,国内外学者对中医药防治胃癌开展了大量的研究工作,其在防治胃癌发病及提高患者生存率方面的独特疗效,受到国内外学者的广泛关注。诱导细胞凋亡已成为中医药防治胃癌的重要机理之一。
泽泻醇B-23-乙酸酯是三萜类纯中药提取物,为泽泻科植物泽泻[Alismaorientalis(Sam) Juzep]的主要成分,具有利尿、降血脂、抗脂肪肝及保肝、抗炎、抗过敏等作用。近年的研究表明其可通过激活caspase-3诱导肝癌细胞凋亡;使肿瘤细胞阻滞在G2/M期诱导淋巴瘤细胞凋亡;逆转P-gp导致HepG2-DR和K562-DR细胞的耐药性,诱导HepG2-DR和K562-DR细胞凋亡。进一步研究显示其可通过线粒体内源性途径诱导耐激素性前列腺癌PC-3细胞的凋亡,同时前列腺癌细胞促凋亡因子bax蛋白表达增加,并发生细胞质向细胞核的转移。对肺癌的研究提示泽泻醇B具有较强的抗恶性肿瘤转移作用。本实验研究了泽泻醇B对SGC7901细胞增殖、细胞周期及调亡的影响,检测细胞凋亡过程中线粒体膜电位及caspase3、caspase9、Bax、Bcl-2及PI3 K/Akt信号转导通路的变化;研究泽泻醇B对胃癌细胞侵袭及迁移的影响,及在抑制胃癌细胞侵袭、迁移过程中,MMP-2、MMP-9活性、蛋白及PI3 K/Akt信号转导通路的变化,阐明泽泻醇B诱导胃癌细胞凋亡,抑制其侵袭及转移的机制,为其进一步临床应用提供理论依据。
方法
一、实验材料
1、人胃腺癌细胞系SGC7901
2、泽泻纯B
3、流式细胞仪检测相关染料
4、Western印迹杂交相关试剂
5、细胞侵袭实验相关材料
二、实验方法
1、MTT检测泽泻纯B对胃癌SGC7901细胞体外增殖的抑制作用
2、PI染色流式细胞仪(FCM)分析细胞周期
3、Annexin V-FITC染色检测细胞早期调亡
4、倒置显微镜、透射电镜观察细胞形态学变化
5、琼脂糖凝胶电泳检测DNA片断化
6、罗丹明-123染色、流式细胞仪检测线粒体膜电位的变化
7、Transwell小室分析泽泻纯B对胃癌SGC7901侵袭、迁移的影响
8、酶谱分析法检测MMP-2、MMP-9活性的变化
9、Western-blot半定量法检测Caspase-3、Caspase-9、Bax和Bcl-2、PI3 K/Akt、MMP-2、MMP-9表达情况
结果
1、MTT法检测结果显示30μmol/L以上浓度泽泻纯B对胃癌SGC7901细胞体外增殖的具有明显的抑制作用,该抑制作用呈明显的时间和剂量依赖性(P＜0.05或P＜0.01)。
2、显微镜下细胞稀疏、变圆、皱缩,一些细胞膜向外鼓出小泡,然后脱落形成凋亡小体;透射电镜,细胞核内异染色质凝聚;细胞核膜溶解,核内异染色质凝聚破碎成多块于胞质中,并见有膜包裹,形成凋亡小体。
3、琼脂糖凝胶电泳见明显的梯形条带,具有时间依赖性(DNA ladder)。
4、Annexin V-FITC/PI荧光染色,流式细胞分析Annexin V/FITC(+),PI(-)细胞即早期凋亡细胞增加(P＜0.05)。
5、PI染色染色流式细胞仪检测细胞周期,S期细胞的比例逐渐降低,G1期细胞的比例逐渐升高,并存在时间依赖性。同时在流式细胞仪DNA组方图上出现典型的凋亡细胞峰(亚G1峰)。
6、罗丹明-123染色流式细胞仪检测线粒体膜电位,泽泻纯处理12小时后SGC7901线粒体膜电位开始下降,随着作用时间的延长下降比例逐渐增加具有时间依赖性。
7、Western-blot半定量法检测Bax表达增高,持续维持在高水平;Bcl-2表达降低,持续维持在低水平
8、Western-blot半定量法检测caspase-3和caspase-9,caspase-3出现17 ku的断裂片段,47 kucaspase-9出现37ku的断裂片断,且二者的活性片断随着泽泻纯作用时间的延长持续维持在高水平;
9、Western-blot半定量法检测磷酸化的PI3 K、Akt(Thr308)表达量降低,而总的PI3 K、Akt的量没有变化。
10、细胞侵袭迁移能力的检测。
应用Transwell小室检测泽泻纯B对胃癌SGC7901细胞侵袭、迁移能力的影响,发现泽泻纯B处理后实验组细胞的侵袭、迁移能力有明显降低,迁移及侵袭过Transwell小室膜的细胞随药物浓度的增加逐渐减少,并具有剂量依赖性
11、酶谱分析法检测泽泻纯B处理前后SGC7901细胞MMP-2、MMP-9酶活性,Western-blot半定量法检测MMP-2,MMP-9蛋白表达量情况,随着药物作用时间的延长MMP-2、MMP-9酶活性逐渐降低,MMP-2,MMP-9蛋白表达量逐渐下降,并具有时间依赖性
结论
1、泽泻纯B对胃癌SGC7901细胞体外增殖具有明显的抑制作用,该抑制作用呈明显的时间和剂量依赖性
2、显微镜下、透射电镜DNA片断化分析及Annexin V-FITC/PI荧光染色流式细胞分析证实了泽泻纯B诱导SGC7901细胞的凋亡。
3、泽泻纯B诱导SGC7901细胞凋亡的信号转导途径中多种基因、蛋白酶以及多种激酶参与了凋亡的调控。Bcl-2、Bax表达的改变,线粒体膜电位的下降,进而caspase-9、caspase-3的激活,PI3K/Akt激酶的激活参与细胞凋亡的调控。
4、泽泻纯B导致SGC7901细胞周期的改变,使SGC7901细胞阻抑在G0/G1期,细胞周期的改变参与了细胞凋亡的发生
5、泽泻纯B抑制SGC7901细胞侵袭和转移,MMP-2、MMP-9活性的下降,蛋白表达的降低在泽泻纯B抑制SGC7901细胞侵袭和转移在过程中起重要的调节作用。
Introduction
Gastric cancer is one of the common malignancies in gastrointestinal tract.Though extensive clinical research has been carried out with numerous combinations of cytotoxic agents,the overall prognosis of advanced gastric cancer still remains poor. Natural products are potential sources of novel anticancer drugs over the decades and contribute a lot to the cancer chemotherapy.Herbal medicines have always held an attraction..
Alisol B acetate is a major ingredient isolated from Alismatis rhizoma and has been used for urological disease in traditional Chinese medicine.In recent years,the pharmacological characterization of alisol B acetate has been identified and several biological activities have been defined,such as the inhibitory effects on lipopolysaccharide-induced mRNA expression of inducible nitric oxide synthase and nitric oxide production,the inhibition of complementary activity and antibody-mediated allergic reaction.Furthermore,it has been demonstrated that alisol B acetate induces cell death in hepatoma and leukemia cells.Furthermore,alisol B acetate induces apoptosis in PC-3 cells via a mitochondria-mediated mechanism with activation of caspase-8,-9 and -3.Alisol B acetate induced Bax up-regulation and nuclear translocation;Up to date,there is no report concerning the role of this natural triterpene on the Gastric Cancer Cell Lines.In order to know the chemopreventive potentials of pseudolaric acid B on gastric carcinoma.,we examinated the effects of alisol B acetate on the growth and apoptosis of the gastric cancer lines SGC7901,and the change of mitchondrial potential and the protein expression of caspase3、caspase9、Bax、Bcl-2 and PI3 K/Akt signal pathway.We analyze MMP-2、MMP-9 activities and protein expression while investigated the effects of Alisol B acetate on the invasive activity and motility of tumor.The data offer a potential mechanism for Alisol B acetate-induced apoptosis in adenocarcinoma SGC7901 cells,suggesting that Alisol B acetate may severve as an effective reagent for the treatment of gastric cancer.
Materials and Methods
Material
1.Human gastric carcinoma cell line SGC-7901
2.Experimental medicine Alisol B acetate
3.Staining reagents for flowcytometry
4.Reagents for Western blot
5.Reagents for invasion and migration
Methods
1、Inhibition of cell proliferation was determined by MTT assay.
2、Cells were stained with PI and cell cycle analysis was performed by Flow cytometry
3、AnnexinV-FITC/PI fluorescent staining was used to tested early cell apoptosis rate.
4、The morphology of SGC7901cells exposed to alisol B acetate for different time was observed first under inverted microscope.Then electronic microscope was used to observe nuclear morphological changes and the apoptotic morphology.
5、DNA fragmentation analysis was assessed by agarose gel electrophoresis.
6、Changes of mitochondrial membrane potential(ΔΨm) were monitored by Rhodamine-123 staining.
7、The effects of Alisol B acetate on invasion and migration of SGC7901 cells were determined in a transwell Boyden chamber
8、Genistein zymography assay were to determine MMP-2 and MMP-9 activities.
9、Western blot was performed to test the influence of Alisol B acetate on Caspase-3、Caspase-9、Bax、Bcl-2、PI3 K/Akt、MMP-2 and MMP-9 protein levels.
Results
1、MTT methods indicated alisol B acetate(over 30μmol/L) had significant growth inhibition effect on SGC7901cells in a dose-and time-dependent manner.
2、Size and number of SGC7901 cells were significantly reduced by incubation with alisol B acetate under inverted microscope.Marked morphological changes of cell apoptosis such as condensation of chromatin and apoptosis body were found clearly using electronic microscope.
3、The characteristic "ladder" of DNA fragments representing integer multiples of the internucleosomal DNA length(about 180～200 bp) was observed by agarose gel electrophoresis in a time-dependent manner.
4、Early Apoptoti cells(AnnexinV/FITC(+),PI(-)) gradually increased in time-dependent manner in SGC7901 cells staining by AnnexinV-FITC/PI fluorescent and analyzing by FCM
5、SGC7901 cells were stained with PI and analyzed by FCM.The percentage of sub-G1 cells in SGC7901 cells was increased in a time-dependent manner.Along with the enhancement of cell growth inhibition,apoptotic cells gradually increased
6、The changes in the membrane potential of the mitochondria were examined by Rhodamine-123 staining.After Alisol B acetate treatment for 12 hours,the cells exhibited a significant alterations inΔΨm,and the percentage of disruption ofΔΨm gradually increased in a time-dependent manner.
7、Western blot analysis of Bcl-2 and Bax expression.Bcl-2 was upregulated while Bax was down-regulated in a time-dependent manner.
8、The proteolytic cleavage of procaspase-3 and-9 also were detected by Western blotting.caspase-3 and caspase-9 were activated,as measured by the appearance of its caspase-3 17 kDa and caspase-9 37 kDa subunit.Caspase-3 and caspase-9 activation increased concomitantly with increased time of alisol B acetate treatment.
9、Protein levels with Western blot analysis the impact of alisol B acetate on PI3K and Akt expressions.Rapid phosphorylations of PI3K and Akt kinase were detected while the total proteins of PI3K and Akt kinase showed no change in alisol B acetate treatment.
10、Effect of alisol B acetate on the Invasion and Migration of SGC7901Cells was observed by Transwell Boyden chamber.Invasion and migration alibility of SGC7901Cells were decreased significantly.Alisol B acetate was able to reduce the number of SGC7901 cells that could penetrated Matrigel membranes in a dose-dependent manner.
11、Western blotting was performed to determine MMP-2 and MMP-9 proteins expression.The expressions of MMP-2 and MMP-9 proteins and activities were significantly decreased in a time-dependent manner
Conclusion
1、Alisol B acetate had significant growth inhibition effect on SGC7901cells in a dose-and time-dependent manner.
2、SGC7901 cells apoptosis inducing by Alisol B acetate were confirmed by inverted microscope、electronic microscope、DNA fragments、AnnexinV-FITC/PI fluorescent staining.
3 Activations of caspase-3 and caspase-9、PI3K/Akt kinase、disruption of the membrane potential of the mitochondria、the changes of Bcl-2、Bax protein level might be involved in alisol B acetate-induced SGC7901 cells apoptosis
4 Alisol B acetate changes the cell cycle phase distribution and arrested SGC7901 cells at G0/G1 phase.The change of the cell cycle phase distribution involved in cells apoptosis
5、Alisol B acetate inhibited invasion and migration of SGC7901 cells.The decreasion of protein level and active enzyme of MMP-2、MMP-9 play a important role in invasion and migration of SGC7901Cells
泽泻醇B-23-乙酸酯是三萜类纯中药提取物,为泽泻科植物泽泻[Alismaorientalis(Sam) Juzep]的主要成分,具有利尿、降血脂、抗脂肪肝及保肝、抗炎、抗过敏等作用。近年的研究表明其可通过激活caspase-3诱导肝癌细胞凋亡;使肿瘤细胞阻滞在G2/M期诱导淋巴瘤细胞凋亡;逆转P-gp导致HepG2-DR和K562-DR细胞的耐药性,诱导HepG2-DR和K562-DR细胞凋亡。进一步研究显示其可通过线粒体内源性途径诱导耐激素性前列腺癌PC-3细胞的凋亡,同时前列腺癌细胞促凋亡因子bax蛋白表达增加,并发生细胞质向细胞核的转移。对肺癌的研究提示泽泻醇B具有较强的抗恶性肿瘤转移作用。本实验研究了泽泻醇B对SGC7901细胞增殖、细胞周期及调亡的影响,检测细胞凋亡过程中线粒体膜电位及caspase3、caspase9、Bax、Bcl-2及PI3 K/Akt信号转导通路的变化;研究泽泻醇B对胃癌细胞侵袭及迁移的影响,及在抑制胃癌细胞侵袭、迁移过程中,MMP-2、MMP-9活性、蛋白及PI3 K/Akt信号转导通路的变化,阐明泽泻醇B诱导胃癌细胞凋亡,抑制其侵袭及转移的机制,为其进一步临床应用提供理论依据。
方法
一、实验材料
1、人胃腺癌细胞系SGC7901
2、泽泻纯B
3、流式细胞仪检测相关染料
4、Western印迹杂交相关试剂
5、细胞侵袭实验相关材料
二、实验方法
1、MTT检测泽泻纯B对胃癌SGC7901细胞体外增殖的抑制作用
2、PI染色流式细胞仪(FCM)分析细胞周期
3、Annexin V-FITC染色检测细胞早期调亡
4、倒置显微镜、透射电镜观察细胞形态学变化
5、琼脂糖凝胶电泳检测DNA片断化
6、罗丹明-123染色、流式细胞仪检测线粒体膜电位的变化
7、Transwell小室分析泽泻纯B对胃癌SGC7901侵袭、迁移的影响
8、酶谱分析法检测MMP-2、MMP-9活性的变化
9、Western-blot半定量法检测Caspase-3、Caspase-9、Bax和Bcl-2、PI3 K/Akt、MMP-2、MMP-9表达情况
结果
1、MTT法检测结果显示30μmol/L以上浓度泽泻纯B对胃癌SGC7901细胞体外增殖的具有明显的抑制作用,该抑制作用呈明显的时间和剂量依赖性(P＜0.05或P＜0.01)。
2、显微镜下细胞稀疏、变圆、皱缩,一些细胞膜向外鼓出小泡,然后脱落形成凋亡小体;透射电镜,细胞核内异染色质凝聚;细胞核膜溶解,核内异染色质凝聚破碎成多块于胞质中,并见有膜包裹,形成凋亡小体。
3、琼脂糖凝胶电泳见明显的梯形条带,具有时间依赖性(DNA ladder)。
4、Annexin V-FITC/PI荧光染色,流式细胞分析Annexin V/FITC(+),PI(-)细胞即早期凋亡细胞增加(P＜0.05)。
5、PI染色染色流式细胞仪检测细胞周期,S期细胞的比例逐渐降低,G1期细胞的比例逐渐升高,并存在时间依赖性。同时在流式细胞仪DNA组方图上出现典型的凋亡细胞峰(亚G1峰)。
6、罗丹明-123染色流式细胞仪检测线粒体膜电位,泽泻纯处理12小时后SGC7901线粒体膜电位开始下降,随着作用时间的延长下降比例逐渐增加具有时间依赖性。
7、Western-blot半定量法检测Bax表达增高,持续维持在高水平;Bcl-2表达降低,持续维持在低水平
8、Western-blot半定量法检测caspase-3和caspase-9,caspase-3出现17 ku的断裂片段,47 kucaspase-9出现37ku的断裂片断,且二者的活性片断随着泽泻纯作用时间的延长持续维持在高水平;
9、Western-blot半定量法检测磷酸化的PI3 K、Akt(Thr308)表达量降低,而总的PI3 K、Akt的量没有变化。
10、细胞侵袭迁移能力的检测。
应用Transwell小室检测泽泻纯B对胃癌SGC7901细胞侵袭、迁移能力的影响,发现泽泻纯B处理后实验组细胞的侵袭、迁移能力有明显降低,迁移及侵袭过Transwell小室膜的细胞随药物浓度的增加逐渐减少,并具有剂量依赖性
11、酶谱分析法检测泽泻纯B处理前后SGC7901细胞MMP-2、MMP-9酶活性,Western-blot半定量法检测MMP-2,MMP-9蛋白表达量情况,随着药物作用时间的延长MMP-2、MMP-9酶活性逐渐降低,MMP-2,MMP-9蛋白表达量逐渐下降,并具有时间依赖性
结论
1、泽泻纯B对胃癌SGC7901细胞体外增殖具有明显的抑制作用,该抑制作用呈明显的时间和剂量依赖性
2、显微镜下、透射电镜DNA片断化分析及Annexin V-FITC/PI荧光染色流式细胞分析证实了泽泻纯B诱导SGC7901细胞的凋亡。
3、泽泻纯B诱导SGC7901细胞凋亡的信号转导途径中多种基因、蛋白酶以及多种激酶参与了凋亡的调控。Bcl-2、Bax表达的改变,线粒体膜电位的下降,进而caspase-9、caspase-3的激活,PI3K/Akt激酶的激活参与细胞凋亡的调控。
4、泽泻纯B导致SGC7901细胞周期的改变,使SGC7901细胞阻抑在G0/G1期,细胞周期的改变参与了细胞凋亡的发生
5、泽泻纯B抑制SGC7901细胞侵袭和转移,MMP-2、MMP-9活性的下降,蛋白表达的降低在泽泻纯B抑制SGC7901细胞侵袭和转移在过程中起重要的调节作用。
Introduction
Gastric cancer is one of the common malignancies in gastrointestinal tract.Though extensive clinical research has been carried out with numerous combinations of cytotoxic agents,the overall prognosis of advanced gastric cancer still remains poor. Natural products are potential sources of novel anticancer drugs over the decades and contribute a lot to the cancer chemotherapy.Herbal medicines have always held an attraction..
Alisol B acetate is a major ingredient isolated from Alismatis rhizoma and has been used for urological disease in traditional Chinese medicine.In recent years,the pharmacological characterization of alisol B acetate has been identified and several biological activities have been defined,such as the inhibitory effects on lipopolysaccharide-induced mRNA expression of inducible nitric oxide synthase and nitric oxide production,the inhibition of complementary activity and antibody-mediated allergic reaction.Furthermore,it has been demonstrated that alisol B acetate induces cell death in hepatoma and leukemia cells.Furthermore,alisol B acetate induces apoptosis in PC-3 cells via a mitochondria-mediated mechanism with activation of caspase-8,-9 and -3.Alisol B acetate induced Bax up-regulation and nuclear translocation;Up to date,there is no report concerning the role of this natural triterpene on the Gastric Cancer Cell Lines.In order to know the chemopreventive potentials of pseudolaric acid B on gastric carcinoma.,we examinated the effects of alisol B acetate on the growth and apoptosis of the gastric cancer lines SGC7901,and the change of mitchondrial potential and the protein expression of caspase3、caspase9、Bax、Bcl-2 and PI3 K/Akt signal pathway.We analyze MMP-2、MMP-9 activities and protein expression while investigated the effects of Alisol B acetate on the invasive activity and motility of tumor.The data offer a potential mechanism for Alisol B acetate-induced apoptosis in adenocarcinoma SGC7901 cells,suggesting that Alisol B acetate may severve as an effective reagent for the treatment of gastric cancer.
Materials and Methods
Material
1.Human gastric carcinoma cell line SGC-7901
2.Experimental medicine Alisol B acetate
3.Staining reagents for flowcytometry
4.Reagents for Western blot
5.Reagents for invasion and migration
Methods
1、Inhibition of cell proliferation was determined by MTT assay.
2、Cells were stained with PI and cell cycle analysis was performed by Flow cytometry
3、AnnexinV-FITC/PI fluorescent staining was used to tested early cell apoptosis rate.
4、The morphology of SGC7901cells exposed to alisol B acetate for different time was observed first under inverted microscope.Then electronic microscope was used to observe nuclear morphological changes and the apoptotic morphology.
5、DNA fragmentation analysis was assessed by agarose gel electrophoresis.
6、Changes of mitochondrial membrane potential(ΔΨm) were monitored by Rhodamine-123 staining.
7、The effects of Alisol B acetate on invasion and migration of SGC7901 cells were determined in a transwell Boyden chamber
8、Genistein zymography assay were to determine MMP-2 and MMP-9 activities.
9、Western blot was performed to test the influence of Alisol B acetate on Caspase-3、Caspase-9、Bax、Bcl-2、PI3 K/Akt、MMP-2 and MMP-9 protein levels.
Results
1、MTT methods indicated alisol B acetate(over 30μmol/L) had significant growth inhibition effect on SGC7901cells in a dose-and time-dependent manner.
2、Size and number of SGC7901 cells were significantly reduced by incubation with alisol B acetate under inverted microscope.Marked morphological changes of cell apoptosis such as condensation of chromatin and apoptosis body were found clearly using electronic microscope.
3、The characteristic "ladder" of DNA fragments representing integer multiples of the internucleosomal DNA length(about 180～200 bp) was observed by agarose gel electrophoresis in a time-dependent manner.
4、Early Apoptoti cells(AnnexinV/FITC(+),PI(-)) gradually increased in time-dependent manner in SGC7901 cells staining by AnnexinV-FITC/PI fluorescent and analyzing by FCM
5、SGC7901 cells were stained with PI and analyzed by FCM.The percentage of sub-G1 cells in SGC7901 cells was increased in a time-dependent manner.Along with the enhancement of cell growth inhibition,apoptotic cells gradually increased
6、The changes in the membrane potential of the mitochondria were examined by Rhodamine-123 staining.After Alisol B acetate treatment for 12 hours,the cells exhibited a significant alterations inΔΨm,and the percentage of disruption ofΔΨm gradually increased in a time-dependent manner.
7、Western blot analysis of Bcl-2 and Bax expression.Bcl-2 was upregulated while Bax was down-regulated in a time-dependent manner.
8、The proteolytic cleavage of procaspase-3 and-9 also were detected by Western blotting.caspase-3 and caspase-9 were activated,as measured by the appearance of its caspase-3 17 kDa and caspase-9 37 kDa subunit.Caspase-3 and caspase-9 activation increased concomitantly with increased time of alisol B acetate treatment.
9、Protein levels with Western blot analysis the impact of alisol B acetate on PI3K and Akt expressions.Rapid phosphorylations of PI3K and Akt kinase were detected while the total proteins of PI3K and Akt kinase showed no change in alisol B acetate treatment.
10、Effect of alisol B acetate on the Invasion and Migration of SGC7901Cells was observed by Transwell Boyden chamber.Invasion and migration alibility of SGC7901Cells were decreased significantly.Alisol B acetate was able to reduce the number of SGC7901 cells that could penetrated Matrigel membranes in a dose-dependent manner.
11、Western blotting was performed to determine MMP-2 and MMP-9 proteins expression.The expressions of MMP-2 and MMP-9 proteins and activities were significantly decreased in a time-dependent manner
Conclusion
1、Alisol B acetate had significant growth inhibition effect on SGC7901cells in a dose-and time-dependent manner.
2、SGC7901 cells apoptosis inducing by Alisol B acetate were confirmed by inverted microscope、electronic microscope、DNA fragments、AnnexinV-FITC/PI fluorescent staining.
3 Activations of caspase-3 and caspase-9、PI3K/Akt kinase、disruption of the membrane potential of the mitochondria、the changes of Bcl-2、Bax protein level might be involved in alisol B acetate-induced SGC7901 cells apoptosis
4 Alisol B acetate changes the cell cycle phase distribution and arrested SGC7901 cells at G0/G1 phase.The change of the cell cycle phase distribution involved in cells apoptosis
5、Alisol B acetate inhibited invasion and migration of SGC7901 cells.The decreasion of protein level and active enzyme of MMP-2、MMP-9 play a important role in invasion and migration of SGC7901Cells
引文
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