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目的:探讨组蛋白去乙酰化酶抑制剂西达本胺(CS055)、DNA甲基转移酶抑制剂地西他滨(DAC)单药和两药联合对急性髓系白血病细胞系U937细胞增殖、凋亡的影响及其可能作用机制。方法:体外培养的U937细胞经CS055(CS055单药组)、DAC(DAC单药组)单药或联合(联合用药组)处理后，并设不加药的阴性对照组，四甲基偶氮唑盐(MTT)法检测细胞增殖抑制率、流式细胞术(FCM)检测细胞凋亡情况，实时荧光定量聚合酶链反应(qRT-PCR)检测DNA甲基转移酶1(DNMT1)mRNA表达，蛋白质印迹法(Western blot)分析乙酰化组蛋白H3、DNMT1的表达。结果:CS055、DAC处理U937细胞后，其增殖抑制率明显增高，呈时间-剂量依赖性。联合用药组的抑制作用较单药组更为明显；对照组、0.25 μmol/L CS055单药组、2.5 μmol/L DAC单药组及联合用药组72 h的凋亡率分别为(0.67±0.12)%、(23.43±0.50)%、(8.47±0.32)%、(32.73±0.42)%，联合组与各单药组比较，凋亡率显著增加；单药组应用CS055和DAC后DNMT1 mRNA和蛋白均表达下调，联合用药组表达下调更明显；单药组应用CS055和DAC后Ac-H3蛋白表达上调，联合组明显高于各单药组。结论:单独应用CS055、DAC对U937细胞均有增殖抑制、促凋亡作用，两药联合应用具有明显的协同效应；其机制可能是组蛋白去乙酰化酶抑制剂有去甲基化作用，去甲基化药物也有组蛋白去乙酰化酶抑制剂作用，两者联合既增加去甲基化作用又增加组蛋白去乙酰化作用。“,”Objective:To investigate the effects of histone deacetylase inhibitor Chidamide (CS055) and DNA methyltransferase inhibitor decitabine (DAC) on proliferation and apoptosis of acute myeloid leukemia cell line U937 and its possible mechanism.Methods:U937 cells were cultured in n vitro and treated with CS055 (CS055 single drug group), DAC (DAC single drug group), combination (combined drug group)and a negative control group. Methyl thiazolyl tetrazolium (MTT) assay was used to detect the proliferation inhibition rate. The apoptosis rate was detected by flow cytometry.The mRNA expression of DNA methyltransferase 1 (DNMT1) was analyzed by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Western blot was used to analyze the expression of acetylated histone H3 and DNMT1.n Results:The proliferation inhibition rate of U937 cells treated with CS055 and DAC increased significantly in a time-dose-dependent manner. The inhibitory effect of the combination group was more obvious than that of the single drug group. Flow cytometry showed that the 72 h apoptotic rates in the control group, 0.25 μ mol/L CS055 group and 2.5 μ mol/L DAC group were (0.67±0.12)%, (23.43±0.50)%, (8.47±0.32)%, (32.73±0.42)%. The apoptotic rate was significantly increased in the combination group compared with the single drug group. qRT-PCR showed that the expression of DNMT1 mRNA was down-regulated after CS055 and DAC treat alone; the down-regulating effect of the combination group was more significant. Western blot showed that the up-regulation of Ac-H3 and the decrease of DNMT1 in the combination group were significantly higher than those in the single drug group.Conclusions:The application of CS055 and DAC alone could inhibit the proliferation and induce apoptosis of U937 cells. The combination of the two drugs has obvious synergistic effect. The mechanism is that histone deacetylase inhibitors have demethylation effects, and demethylation drugs also have the effect of histone deacetylase inhibitors, which in combination increases demethylation and increases histone deacetylation.