二甲双胍抑制急性髓系白血病细胞增殖

Inhibitory Effect of Metformin on Proliferation of Acute Myeloid Leukemia Cells

目的探讨降糖药物二甲双胍对人急性髓系白血病细胞系U937细胞增殖的作用。方法将浓度梯度的二甲双胍(0、5、10、20、40、60 mmol·L^(-1))分别作用于U937细胞24、48 h,采用CCK-8试剂盒检测U937细胞活力,Annexin-V/PI assay试剂盒检测U937细胞凋亡率,JC-1检测U937细胞线粒体膜电位下降水平。同时基于细胞活力试验检测结果,将上述浓度梯度的二甲双胍分别作用于U937细胞48 h,采用Western blot检测Bcl-2蛋白表达水平。结果二甲双胍作用24 h对U937细胞增殖抑制作用较弱、无明显杀伤作用;作用48 h对U937细胞有抑制细胞生长、促进凋亡、降低线粒体膜电位作用,同时显著降低U937细胞Bcl-2蛋白水平。结论二甲双胍可杀伤人急性髓系白血病细胞系U937细胞。二甲双胍抗白血病作用可能与其下调线粒体膜电位、抑制Bcl-2蛋白表达有关。

Objective To investigate the inhibitory effect of metformin on proliferation of human leukemia U937 cells.Methods U937 cells were incubated with different concentrations of metformin(0,5,10,20,40 and 60 mmol·L^(-1))for 24 and 48 h.Cell viability,apoptosis and mitochondrial membrane potential were detected by CCK-8,Annexin-V/PIandJC-I assays,respectively.The expression of Bcl-2 was measured by Western blot.Results Treatment with metformin for 24 h had no obviously inhibitory effect on the proliferation of U937 cells.However,48 h of incubation with metformin significantly inhibited proliferation,promoted apoptosis,decreased mitochondrial membrane potential,and down-regulated Bcl-2 expression in U937 cells.Conclusion Metformin can induce apoptosis in U937 cells via decreasing mitochondrial transmembrane potential and Bcl-2 expression.