曲古抑菌素A促进As_2O_3诱导HL-60细胞分化与分子机制的研究  

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

作　　者：毕高峰[1] 刘佳宁[1] 温培娥[1] 杨炜华[1] 任霞[1] 唐天华[1] 谢超[1] 董伟[1] 姜国胜[1] 

机构地区：[1]山东省医学科学院基础医学研究所山东省现代医用药物与技术重点实验室,山东济南250062

出　　处：《中华肿瘤防治杂志》2007年第9期653-656,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省优秀中青年科学家基金项目(03BS033);山东省自然科学基金重点项目(Z2004C08)

摘　　要：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cyclinD3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24h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,cyclinD3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cyclinD3和细胞周期蛋白依赖性激酶抑制剂p21的表达变化有关。OBJECTIVE：To study if trichostatin A facili tares 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 differentia tion of the cells was detected by FCM. The expressions of mR NA 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 Da. 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.

关 键 词：白血病 曲古抑菌素A 砷剂 氧化物 HL-60细胞 诱导分化 协同作用 

分 类 号：R733.7[医药卫生—肿瘤]