地西他滨联合全反式维甲酸对HL-60细胞增殖及分化的影响

摘要

目的 探讨地西他滨(DCA)和全反式维甲酸(ATRA)对急性早幼粒细胞白血病(APL)细胞株HL-60增殖及分化的影响.方法 HL-60细胞经不同浓度DCA、ATRA、两药单用或联合处理后,用四甲基偶氮唑盐(MTT)比色法观察不同浓度DCA和ATRA对HL-60细胞增殖活性的影响,用硝基四氮唑蓝(NBT)还原试验和流式细胞术观察不同浓度DCA和ATRA对HL-60细胞分化的影响.结果 DCA和ATRA均能够抑制HL-60细胞的增殖,呈时间、剂量依赖性(P＜0.01),并且3.2 mmol· L-1 DCA联合1×10-6mol·L-1ATRA组与单用两药比较,其增殖抑制的协同作用明显增强(P＜0.05).DCA和ATRA均能够促进HL-60细胞的分化,3.2 mmol·L-1DCA和1×10-6mol·L-1ATRA的促分化能力最强,并且两药联合应用具有协同促分化作用.结论 DCA和ATRA均可以抑制HL-60细胞的增殖以及促进HL-60细胞分化,两者联合应用有协同作用.%Objective To investigate the effect of demethylation agent decitabine (DCA) and all-trans retinoic acid (ATRA) on proliferation and differentiation of acute promyelocytic leukemia (APL) cell line HL-60. Methods HL-60 cells were co-cultured with different concentrations of DCA and/or ATRA. The proliferation activity was detected by MTT assay in HL-60 cells. The differentiation ability of HL-60 cells was observed by nitro-blue tetrazolium (NBT) reduction test and flow cytometry. Results The proliferation of HL-60 cells was inhibited by DCA and ATRA in a dose and time dependent manner (P< 0.01). The concentration of 3.2 mmol·L-1 DCA combined with l×l06 mol·L-1 ATRA showed a more obvious inhibition on proliferation of HL-60 cells compared with that of DAC or ATRA alone (P < 0.05). Both DCA and ATRA could promote differentiation of HL-60 cells. The strongest ability in promoting differentiation was found in 3.2 mmol · L-1 DCA group and 1 × 10-6 mol · L-1 ATRA group.The combination of DCA and ATRA had synergistic effect. Conclusion Both DCA and ATRA can inhibit the proliferation and promote the differentiation of HL-60 cells,and the combination of DCA and ATRA had synergistic effect.