二甲双胍对人胃癌细胞株MKN45增殖和迁徙的影响  

Effect of Metformin on Proliferation and Migration of Human Gastric Cancer Cell Line MKN45

作　　者：薛知新[1] 赵丹瑜[1] 许慈[1] 孙萍胡[1] 姚静静[1] 钟捷[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院消化科

出　　处：《胃肠病学》2010年第5期280-283,共4页Chinese Journal of Gastroenterology

摘　　要：背景：近年发现二甲双胍具有潜在抑制肿瘤的作用,但其在消化系肿瘤尤其是胃癌中的研究较少.目的：研究二甲双胍对人胃癌细胞株MKN45增殖和迁徙的影响,并初步探讨其可能机制.方法：体外培养人胃痛细胞株MKN45,予10 mmol/L二甲双胍进行干预（联合或不联合5-氟尿嘧啶）,以MTT法检测细胞存活率,流式细胞仪检测细胞凋亡、线粒体膜电位,细胞划痕实验检测迁徙速率,RT-PCR检测AMPKα1、cyclin D1、Bc1-2、Bax、MMP-2、MMP-9 mRNA表达.结果：与对照组相比,二甲双胍作用后,MKN45细胞存活率显著降低,并呈浓度-时间依赖性,细胞凋亡率显著增加,线粒体膜电位显著下降,平均迁徙速率显著降低,cyclin D1、MMP-2、MMP-9 mRNA表达均显著减少,Bc1-2、BaxmRNA表达显著增加但两者之比降低,AMPKα1 mRNA表达无明显差异.二甲双胍与5-氟尿嘧啶联用对MKN45细胞的存活率无明显协同作用.结论：二甲双胍能抑制人胃癌细胞株MKN45增殖、迁徙,可通过改变线粒体膜通透性促进细胞凋亡.Background： Metformin has recently been shown to have potential antitumor effect, but the studies on digestive system tumors especially the gastric cancer are rare. Aims： To investigate the effect of metformin on proliferation and migration of human gastric cancer cell line MKN45, and to appraise the possible potential mechanism. Methods： Cultured human gastric cell line MKN45 was incubated with 10 mmol/L metformin with or without 5-fluorouracil （5-FU）. Survival rate of MKN45 cells was determined by MTT assay. Apoptosis and mitoehondrial membrane potential were measured by flow eytometry. Migration velocity was determined by scratch assay. Expressions of AMPKα1, cyclin D1, Bcl-2, Bax, MMP-2 and MMP-9 mRNA were determined by RT-PCR. Results： Compared with the control, metformin treated MKN45 cells had lower survival rate in a dose- and time-dependent manner and higher apoptosis rate, and had lower mitoehondrial membrane potential and migration velocity. Expressions of cyclin D1, MMP-2, MMP-9 mRNA were down-regulated, whereas expressions of Bcl-2, Bax mRNA were up-regulated, but the Bcl-2/Bax ratio was decreased. The expression of AMPKctl mRNA was not significantly altered. No synergistic effect on survival rate of MKN45 cells was observed when metformin was combined with 5-FU. Conclusions： Metformin can inhibit the proliferation and migration of human gastric cancer cell line MKN45, and induce apoptosis through alteration of mitochondrial membrane potential.

关 键 词：二甲双胍 胃肿瘤 细胞增殖 细胞凋亡 迁徙 

分 类 号：R735.2[医药卫生—肿瘤]