【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。更多还原

【Abstract】 Objective: To study the effect of metformin on proliferation,cell cycle and apoptosis of U937 cells. Methods: U937 cells were treated with different concentrations of metformin,collected 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 cytometry( FCM). The expression of Bcl-2,Bax,pAMPK,p53 were determined by Western blot. Results: The proliferation of U937 cells was inhibited by metformin in a time-and dosedependent manner. Metformin-treated cells were arrested at G0/G1 phase,the cell frequency at G0/G1 phase was increased in a timeand dose-dependent manner. Metformin also induced cell apoptosis in a dose-dependent manner. It showed that 20 mmol/L metformin 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 metformin treatment. Conclusion: Metformin 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.更多还原