维奈克拉联合地西他滨、阿柔比星对急性髓系白血病细胞增殖和凋亡的影响

Influence of venetoclax combined with decitabine and/or aclarubicin on the proliferation and apoptosis of acute myeloid leukemia cells

目的:观察维奈克拉(venetoclax,ABT-199)联合地西他滨(decitabine,DAC)、阿柔比星(aclarubicin,ACM)对急性髓系白血病(acute myeloid leukemia,AML)细胞株HL60、KG-1细胞增殖和凋亡的影响。方法:CCK-8法检测不同浓度ABT-199、DAC、ACM单药及ABT-199+DAC、ABT-199+ACM、ABT-199+ACM+DAC 3种药物联合方式对HL60、KG-1细胞增殖的影响,使用Compusyn软件分析药物联合是否具有协同作用;流式细胞术检测上述单药及药物联合对HL60、KG-1细胞凋亡比例和细胞周期分布的影响。结果:ABT-199、DAC、ACM单药均抑制HL60、KG-1细胞增殖。相比单药ABT-199,3种药物联合方式均显著增强对HL60、KG-1细胞增殖的抑制作用,且均具有协同作用。ABT-199联合用药明显促进HL60、KG-1细胞凋亡。DAC、ABT-199+DAC、ABT-199+ACM+DAC可促使HL60、KG-1细胞周期阻滞于G2/S期。结论:ABT-199联合DAC、ACM抑制AML细胞增殖且具有协同作用,可促进AML细胞凋亡和细胞周期阻滞。

Objective:To investigate the effects of venetoclax(ABT-199)combined with decitabine(DAC)and/or aclarubicin(ACM on the proliferation and apoptosis of acute myeloid leukemia(AML)cell lines(HL60 and KG-1). Methods:HL60 and KG-1 were treated with different concentrations of ABT-199,DAC,ACM,ABT-199+DAC,ABT-199+ACM and ABT-199+ACM+DAC. The cell proliferation was determined by CCK-8 method. Compusyn software was used to analyze whether the drug combinations had synergistic effect. The apoptosis and cell cycle were detected by flow cytometry(FCM). Results:ABT-199,DAC and ACM inhibited the growth of HL60 and KG-1 respectively. The three ways of drug combinations significantly inhibited the cell proliferation of HL60 and KG-1,compared with ABT-199 alone,and all had synergistic effect. The combinations of ABT-199 significantly induced the apoptosis of HL60 and KG-1. The cell cycle was arrested at G2/S phase in HL60 and KG-1 cells treated by DAC,the combination of ABT-199 and DAC,or the combination of ABT-199,ACM and DAC. Conclusion:ABT-199 combinations significantly inhibited the proliferation of AML cell lines and had synergistic effect. ABT-199 combined with ACM and DAC promoted the apoptosis and arrested the cell cycle of AML cells.