国际医药卫生导报2019，Vol.25Issue(2)：193-198,6.DOI:10.3760/cma.j.issn.1007-1245.2019.02.008
二甲双胍联合顺铂抑制神经胶质瘤细胞增殖及其机制初步探讨
Effect of metformin in combination with cisplatin on the proliferation of glioma cells and its mechanisms
摘要
Abstract
Objective To observe the effect of metformin on U251 cell proliferation,apoptosis,and the growth of glioma in nude mice.Methods Metformin in combination with cisplatin were used to treated the U251 cells,and the cell viability was assayed by MTT methods.Cell cycle,apoptosis rate were assayed by flow cytometry.The expression of apoptotic related proteins (Bcl-2,Bcl-xl,Bax,PARP,et al) were detected by western-blotting.Nude mice were transplanted with U251 cells,and tumor growth inhibition rate by metformin combined with or without cisplatin were detected.Results Compared with the control group,metformin combined with or without cisplatin could inhibit the proliferation of U251 cells in a dose-and time-dependent manner.After U251 cells were treated with 10 mM metformin for 48 h,the growth cycle was arrested in S phase,the apoptosis rate was (20.57±3.16)％.The expression of anti-apoptotic protein Bcl-2,Bcl-xl were down-regulated after metformin treatment,while the pro-apoptotic protein Bax was significantly increased.In vivo studies,the inhibition rates in the metformin-treated group,cisplatin-treated group,and cisplatin combined with metformin-treated group were 39.22％,52.97％,and 71.55％,respectively.The inhibition rates in the above three groups were all higher than that in the control group.The difference between the two groups was statistically significant (metformin-treated group vs.control group,cisplatin combined with metformin-treated group vs.cisplatin-treated group,P＜0.01).However,metformin could not inhibit the glioma metastasis in vivo.Conclusion Metformin inhibits the proliferation of U251 cells,enhances the sensitivity of glioma U251 cells to cisplatin,and induces apoptosis via the mitochondria mediated apoptotic signaling pathway in vitro.关键词
神经胶质瘤/二甲双胍/细胞凋亡/线粒体介导Key words
Neuroglioma/Metformin/Cell apoptosis/Mitochondrial-mediated引用本文复制引用
王廷瑞,孔令贵,庞丽,刘观斌,崔向芹..二甲双胍联合顺铂抑制神经胶质瘤细胞增殖及其机制初步探讨[J].国际医药卫生导报,2019,25(2):193-198,6.基金项目
山东省中医药科技发展计划项目(2015-497)Shandong Science and Technology Development Project of Traditional Chinese Medicine (2015-497) （2015-497）
