转化生长因子β1／SMAD信号通路在六亚甲基二乙酰胺抑制K562细胞增殖中的作用  

Effect of TGF- β1/SMAD signaling pathway on K562 cells growth inhibition caused by HMBA

作　　者：苏恩裕[1] 温培娥[1] 任霞[1] 孙晓柏[1] 张恒兰[1] 唐天华[1] 任海全[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,济南250062

出　　处：《国际肿瘤学杂志》2010年第4期312-315,共4页Journal of International Oncology

基　　金：国家自然科学基金资助项目（30771103）;山东省1020工程杰出学科带头人基金资助项目（[2008]2号）;山东省自然科学基金资助项目（Y2008C165）

摘　　要：目的探讨转化生长因子β1（TGF-β1）／SMAD信号通路在六亚甲基二乙酰胺（HMBA）抑制K562细胞增殖中的作用。方法采用HMBA诱导K562细胞分化模型后，四甲基偶氮唑盐（MTT）实验和流式细胞术分别检测HMBA对K562细胞的增殖和细胞周期作用，逆转录-聚合酶链反应（RT-PCR）检测TGF-β1、SMAD3、SMAD4和亲嗜性病毒整合位点1（EVI1）在基因水平上相对表达量的变化趋势。结果HMBA能抑制K562细胞增殖并促进其分化，作用程度随时闻延长或剂量加大而增大，作用72h时半数抑制浓度（IC50）为2mmol／L。K562细胞经2mmol／LHMBA作用72h内，G0—G1期细胞百分率逐渐增高；TGF—β1、SMAD3和SMAD4在mRNA水平的相对表达量逐渐增高，而EVI1在mRNA水平的相对表达量逐渐降低。结论HMBA通过TGF-β1／SMAD信号通路抑制K562细胞增殖。Objective To investigate the effect of TGF-β1/SMAD signaling pathway on K562 cells growth inhibition caused by HMBA. Methods After establishing the in vitro differentiation model with HMBA on K562 ceils, the MTT assay was used to detect the proliferation of K562 cells, the cell cycle profile was detected by flow cytometry, and the mRNA expression of TGF-β1, SMAD3, SMAD4 and EVIl was measured by RT-PCR assay. Results HMBA could inhibit the proliferation and promote the differentiation of K562 cells obviously, which was time and concentration-dependent, and the 72 h corresponding IC50 was about 2 mmol/L. Within 72 h, flow eytometry assay indicated that the ration of GO -G1 phase cells was up-regulated, and the results of RT-PCR showed that relative mRNA expression of TGF-β1, SMAD3 and SMAIM at mRNA level was increased gradually while that of EVIl was decreased gradually. Conclusion HMBA can inhibit K562 cells proliferation through TGF-β1/SMAD signaling pathway.

关 键 词：转化生长因子Β1 SMAD蛋白质类 K562细胞 六亚甲基二乙酰胺 

分 类 号：R730.2[医药卫生—肿瘤]