地西他滨联合三氧化二砷抑制急性髓系白血病细胞系增殖和促进凋亡

Decitabine combined with arsenic trioxide inhibits proliferation and promotes apoptosis of acute myeloid leukemia cell lines

目的探讨地西他滨(DAC)联合三氧化二砷(ATO)对急性髓系白血病(AML)细胞增殖、凋亡的影响及潜在分子机制。方法DAC和ATO单药或联合处理AML细胞系,CCK8法检测细胞活力;Compusyn软件分析两药联合的协同效应;流式细胞术分析细胞凋亡率及细胞周期分布;Western blot检测凋亡相关蛋白多聚ADP核糖聚合酶(PARP)和磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)蛋白表达。结果DAC及ATO单药以浓度依赖的方式抑制AML细胞增殖,两药联合可协同抑制AML细胞增殖、诱导细胞凋亡和周期阻滞(P<0.05)。两药联合显著降低AML细胞PI3K及Akt的磷酸化水平(P<0.05)。结论DAC联合ATO可能通过抑制PI3K/Akt通路发挥抗AML效应,为两药联合临床治疗AML提供一定理论依据。

Objective To investigate the effects of decitabine(DAC)combined with arsenic trioxide(ATO)on proliferation and apoptosis of AML cells and its underlying molecular mechanism.Methods AML cell lines were treated with DAC and ATO alone or in combination.CCK8 was used to detect cell viability;Compusyn software was used to analyze thesynergistic effects of the combination treatment;Flow cytometry was applied to determine the apoptosis and cell cycle distribution;Western blot was applied to detect the expressions of poly(ADP-ribose)polymerase(PARP),c-PARP,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(Akt)and p-Akt.Results DAC and ATO alone inhibited AML cell proliferation in a concentration-dependent manner.The combination of the two drugs significantly inhibited cell proliferation,induced apoptosis and cycle arrest of AML cells(P<0.05).Combination therapy reduced the phosphorylation level of PI3K and Akt(P<0.05).Conclusions DAC combined with ATO may have anti-AML effect by inhibiting PI3K/Akt pathway,which provides new theoretical basis of DAC+ATO strategy for AML.