二甲双胍与三氧化二砷对KG1a细胞增殖的抑制作用

Inhibitory Effect of Metformin and Arsenic Trioxide on KG1a Cell Proliferation

目的:探讨二甲双胍协同三氧化二砷对急性髓系白血病KG1a细胞增殖的影响及其可能的机制。方法:采用CCK-8法检测二甲双胍、三氧化二砷以及联合应用对KG1a细胞的杀伤作用;Annexin V-FITC/PI双染法流式细胞术检测应用二甲双胍协同三氧化二砷对KG1a细胞凋亡的影响;Western blot检测胞内凋亡、自噬相关蛋白的表达。结果:二甲双胍与三氧化二砷联合及单独应用均可抑制KG1a细胞增殖,诱导KG1a细胞凋亡,联合用药组增殖抑制率及凋亡率高于单独用药组(P<0.05)。联合用药诱导KG1a细胞中Caspase 8和P62蛋白表达上调且高于单药组(P<0.05)。结论:二甲双胍能协同三氧化二砷杀伤KG1a细胞,其作用机制可能与诱导凋亡和增强自噬有关。

Objective:To investigate the effect of metformin and arsenic trioxide on KGla cells proliferation of acute myeloid leukemia and its possible mechanism.Methods:CCK-8 method was used to detect the killing effect of metformin,arsenic trioxide and combined application on KGla cells.Annexin V-FITC/PI Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KGla cells.Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein.Results:Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KGla cells and induce apoptosis of KGla cells,and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P<0.05).The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P<0.05).Conclusion:Metformin can synergize with arsenic trioxide to kill KGla cells,and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.