【摘要】 目的探讨三氧化二砷(As2O3)对肝癌HepG2细胞增殖的影响及其与细胞周期素依赖性激酶抑制剂(CDKI)p27kip1和p27kip1相关蛋白FOXO3a的关系。方法体外培养人肝癌细胞株HepG2经2μmol/L As2O3处理72 h,用流式细胞仪检测细胞周期变化,并采用核浆分离、Western blot技术及细胞免疫荧光技术检测该过程中p27kip1和FOXO3a在HepG2细胞中的表达变化和亚细胞定位情况。结果与对照组比较,As2O3使HepG2细胞周期阻滞在G2/M期,并诱导凋亡。As2O3作用后,HepG2细胞的p27kip1蛋白和FOXO3a蛋白总量也增加,并且p27kip1的表达变化与FOXO3a的表达水平高低及核-胞浆易位相关。结论 As2O3可能通过上调FOXO3a的表达影响p27kip1基因的转录,从而调控肝癌细胞的增殖。更多还原

【Abstract】 Objective To investigate the effects of arsenic trioxide(As2O3) on cell cycle arrest and to assess whether FOXO3a might be involved in the up-regulation of cyclin-dependent kinase(CDKI)-p27kip1 in As2O3-treated human hepatomacellular carcinoma(HCC) HepG2 cells.Methods Cultured in vitro,HCC HepG2 was treated for 72 h with 2 μmol/L arsenic trioxide.The cell cycle was detected by flow cytometry(FCM).The expression and localization of p27kip1,FOXO3a were detected by subcellular fractionaion,Western blot and immunoflurescence.Results HepG2 cell cycle was arrested in G2/M by As2O3,compared with the untreated control cell.A striking increase in FOXO3a expression and a similar increase in p27kip1 expression were found in As2O3-treated HepG2 cell.Conclusion Arsenic trioxide enhances FOXO3a expression intensify gene transcription of p27kip1,and may participate in regulating growth of human hepatoma cells through interfering with the function of p27kip1.更多还原