二甲双胍对U937细胞增殖、周期及凋亡的影响  

Effect of metformin on proliferation,cell cycle and apoptosis of U937 cells

作　　者：李君茹[1] 李会方[1] 周嘉[1] 张丽芸[1] 卢晓[1] 左大明[1] 陈政良[1] 

机构地区：[1]南方医科大学基础医学院免疫教研室,广州510515

出　　处：《中国免疫学杂志》2017年第9期1315-1319,共5页Chinese Journal of Immunology

摘　　要：目的:探究二甲双胍(metformin)对U937细胞增殖、周期及凋亡的影响。方法:以U937细胞为研究对象,予不同浓度的二甲双胍处理,分别在24、48和72 h收集细胞。CCK-8法检测细胞增殖情况,流式检测细胞凋亡及细胞周期,并使用Western blot方法检测促凋亡蛋白Bax、抑凋亡蛋白Bcl-2、p-AMPK、p53的表达情况。结果:CCK8结果显示二甲双胍抑制U937的增殖,且呈时间-剂量依赖性。流式结果显示二甲双胍处理后细胞周期停滞在G0/G1期,G0/G1期细胞比例的增加呈时间-剂量依赖性。二甲双胍可诱导细胞凋亡,且凋亡率呈剂量依赖性;二甲双胍浓度为20 mmol/L时,凋亡率呈时间依赖性。Western blot结果显示二甲双胍处理后,p-AMPK、p53、Bax的表达上调,而Bcl-2的表达下调。结论:二甲双胍能抑制U937细胞的增殖,阻滞细胞周期在G0/G1期,诱导细胞凋亡;其机制可能与其上调胞内促凋亡蛋白Bax的表达、下调抑凋亡蛋白Bcl-2的表达、激活AMPK/p53通路有关。ObjectiveTo study the effect of metfor^nin on proliferation, cell cycle and apoptosis of U937 cells. Methods： U937 cells were treated with different concentrations of metformin,conected cells in 24,48 and 72 hours. Subsequently,cell proliferation was assessed by CCK-8 assay,and the cell cycle and apoptosis were analyzed by flow c.ytometry （FCM）. The expression of Bcl-2, Bax, p- AMPK, p53 were determined by Western blot. Results： The proliferation of U937 cells was inhibited by meformin in a time-and dose- dependent manner. Metformin-treated cells were arrested at G0/G1 phase,the cell frequency at G0/G1 phase was increased in a time- and dose-dependent manner. Metformin also induced cell apoptosis in a dose-dependent manner. It showed that 20 mmoL/L metfomiin induced cell apoptosis in a time-dependent manner. The expression of p-AMPK, p53, Bax was up-regulated while Bcl-2 expression was down-regulated after metfomiin treatment Conclusion： Meformin could inhibit the U937 cell proliferation, block the cell cycle at G0/G1 phase,and induce cell apoptosis,which may partially be attribute to the up-regulation of Bax, down-regulation of Bcl-2, activation of AMPK/p53 signaling.

关 键 词：二甲双胍 U937细胞 增殖 细胞周期 凋亡 AMPK/p53 

分 类 号：R73[医药卫生—肿瘤]