二氯乙酸对急性髓系白血病细胞株U937细胞凋亡的影响及其机制的研究

Effect of dichloroacetate on apoptosis of human leukemia cell line U937

目的探讨二氯乙酸对急性髓系白血病细胞株U937凋亡的影响及其相关机制。方法急性髓系白血病细胞株U937细胞为研究对象,采用不同浓度的二氯乙酸对其进行处理后,测定不同作用时间下的相关指标,包括用CCK-8法测定细胞增殖活性变化;流式细胞术检测活性氧簇(ROS)的变化及细胞凋亡情况;蛋白免疫印迹法检测细胞凋亡通路相关蛋白Cleaved-caspase-3、Cleaved-PARP的表达。结果二氯乙酸呈时间-剂量依赖性抑制U937细胞生长。二氯乙酸处理24 h后,U937细胞ROS生成明显增多,伴细胞凋亡增加明显(P均<0.05)。结论二氯乙酸可以抑制U937细胞增殖并诱导其凋亡。细胞的凋亡机制可能与细胞代谢途径改变导致的ROS增加有关。

Objective To study the effect of DCA on apoptosis of human leukemia cell line U937 and possible mechanism. Methods The leukemia cell line U937 cells were cultured with various concentra-tion of dichloroacetate in different time duration. The proliferation ability was measured by cck8 assay. The re-active oxygen species （ROS） and apoptosis rate were detected by flow cytometry. The expression of cleaved-easpase 3 and cleaved-PARP were shown by western blot. Results The proliferation of U937 cells could be inhibited by DCA. The apoptosis of U937 cells were increased and could be caused by up-regulated ROS when treated with DCA for 24 h. Conclusions The proliferation of U937 cells could be inhibited by DCA. Mito-chondrial pathway may be involved in the apoptosis of U937 cells by DCA. ROS may played an important role in apoptosis of U937 ceils.