曲古抑菌素A促进As2O3诱导HL-60细胞分化与分子机制的研究

目的：研究曲古抑菌素A能否促进小剂量三氧化二砷（As2O3）诱导HL-60细胞分化并对其机制进行初步探讨.方法：用MTT实验测定药物对细胞增殖的变化;流式细胞仪检测细胞表面CD11b表达率观察药物对细胞的分化作用; RT-PCR方法检测p21和cyclin D3在mRNA水平的表达变化.结果：HL-60细胞经曲古抑菌素A和（或）小剂量As2O3作用24 h后,联合用药组较单用As2O3组能明显抑制细胞增殖,促进细胞分化,p21在mRNA水平表达增加,cyclin D3在mRNA水平表达降低.结论：曲古抑菌素A能促进小剂量As2O3诱导HL-60细胞的分化,其机制可能与细胞周期蛋白cyclin D3和细胞周期蛋白依赖性激酶抑制剂p21的表达变化有关.

Molecular mechanism of trichostatin A facilitating arsenic trioxide to induce HL-60 cells differentiation

OBJECTIVE:To study if trichostatin A facilitates arsenic trioxide to induce HL-60 cells differentiation and explore the underlying mechanism.METHODS:The alteration in the cell proliferation was determined by MTT experiment.CD11b on cellular surface was inspected,and the differentiation of the cells was detected by FCM.The expressions of mRNA of p21 and cyclin D3 in HL-60 cells after exposure to TSA and(or)As2O3 were assayed by semi-quantitative RT-PCR.RESULTS:TSA combined with As2O3 inhibited the proliferation and induced the differentiation more obviously than single use of As2O3,and up-regulated the mRNA expression of p21 but down-regulated the expression of cyclin D3.CONCLUSION:TSA has synergistic effect with As2O3 in inducing HL-60 cells,differentiation and it is associated with the change of expressions of p21 and cyclin D3.