二甲双胍对U937 细胞增殖、周期及凋亡的影响

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。

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

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,p-AMPK,p53 were determined by Western blot.Results: The proliferation of U937 cells was inhibited by metformin 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 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.