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  

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

作　　者：杨炜华[1] 温培娥[1] 谢超[1] 乔高娟[1] 任霞[1] 任海泉[1] 唐天华[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省医药卫生肿瘤免疫与中药免疫重点实验室,济南250062

出　　处：《国际肿瘤学杂志》2008年第3期228-231,共4页Journal of International Oncology

基　　金：国家自然科学基金资助项目（30771103）;科技部中瑞政府间合作项目（AM15B;1）;山东省自然科学基金重点项目（Z2004C08）;山东省1020工程杰出学科带头人基金资助项目;山东省优秀中青年科学家科研奖励基金资助项目（2007BS03002）;山东省自然科学基金资助项目（Y2005C39）

摘　　要：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。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 GO 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/Bcl-2 ratio was up-regulated. Conclusion Synergetic effect by As2O3 and TSA is remarkable in inducing apoptosis of HL-60 cells. Cell cycle arrest and Bax/Bcl-2 ratio play an important role in apoptosis of HL-60 cells induced by As2O3, TSA or their combination.

关 键 词：HL-60细胞 砷剂 组蛋白脱乙酰基酶类 细胞凋亡 

分 类 号：R733.7[医药卫生—肿瘤]