三氧化二砷和曲古抑菌素A协同诱导HL-60细胞凋亡的作用及分子机制研究

目的 探讨三氧化二砷(As2O3)和曲古抑菌素A(TSA)在体外诱导急性早幼粒白血病细胞HL-60凋亡过程中的协同作用.方法 采用MTT法检测As2O3和(或)TSA对HL-60细胞增殖的影响,流式细胞术检测细胞周期和细胞凋亡,逆转录-聚合酶链反应(RT-PCR)检测凋亡相关基因Bax和Bcl-2的表达.结果 As2O3和TSA联用较单独用药能明显抑制细胞,引起细胞周期阻滞和凋亡,Bax基因表达升高,Bcl-2基因表达降低,Bax/Bcl-2比值升高.结论 As2O3和TSA均能够引起HL-60凋亡,二者具有协同效应,其机制是引起细胞周期阻滞,且上调Bax与Bcl-2比值.

Synergetic effect of arsenic trioxide and Trichostatin A during inducing apoptosis of HL-60 cell and the molecular mechanisms

Objective To detect the synergetic effect and mechanism of arsenic trioxide(As2O3)and Trichostatin A(TSA)during inducing apoptosis of HL-60 cells.Methods MTT method was used to test the proliferation of HL-60 cells.Cell cycle and apoptosis were detected by FCM.Semi-quantitative RT-PCR was used to detect the mRNA expression of Bax and Bcl-2 in the cells treated by As2O3 and(or)TSA.Results As2O3 combined with TSA could inhibit proliferation and induce cell cycle arrest at G0 and G1.The percent of apoptosis induced by combination of As2O3 and TSA was obviously higher than that of either As2O3 or TSA.Bax gene expression was increased,while Bcl-2 gene expression was decreased,Bax/Bel-2 ratio was up-regulated.Conclusion Synergetic effect by As2O3 and TSA is remarkable in inducing apoptosis of HL-60 cells.Cell cycte arrest and Bax/Bcl-2 ratio play an important role in apoptosis of HL-60 cells induced by As2O3,TSA or their combination.