To study the effects on apoptosis by PHI in K562/G01 cell line and to explore its potential histone modulative mechanisms. Methods AnnexinV/PI assays were used to evaluate cell apoptosis in K562/G01 cell lines. The expression levels of Bcl-2 and procaspase-3 proteins,the changes of histone acetylated H3 and H4, histone methylated H3K4 and H3K9 in K562/G01 cells treated with PHI were detected by Western Blot. Results PHI induced rnapoptosis in K562/G01 cells in a concentration-dependent manner. Along with the concentration adding, the ratio of apoptosis was raising. The control group, 10 μmol/L PHI group, 20 μmol/L PHI group and 40 μmol/L PHI group, the corresponding apoptosis ratio was (3. 76 ± 1. 46) %, (8.89 ± 2.31)%, (18.10 ± 3.56)%, (35. 35 ± 3. 70) %, the difference was statistically significant (P<0. 05). PHI down-regulated proteins of Bcl-2, rnprocaspase-3 and induced an accumulation of histone acetylated H3, H4, and increased histone methylation H3K4 and decreased methylated H3K9. Conclusions PHI could induce apoptosis in K562/G01 cell line. The effects may be associated with the modulations of histone acetylation and methylation.%目的 体外观察异硫氰酸苯己酯(PHI)对人慢性粒细胞白血病伊马替尼耐药的K562/G01细胞株的凋亡的影响,初步探讨其可能的组蛋白调控机制.方法 流式细胞仪检测PHI作用前后K562/G01细胞凋亡的变化;Western Blot检测PHI处理K562/G01细胞株后凋亡相关蛋白Bcl-2,procaspase-3,组蛋白H3、H4乙酰化状态,组蛋白H3K4、H3K9甲基化状态的变化.结果 PHI可以诱导K562/G01细胞凋亡,且呈浓度依赖性.PHI终浓度为0,10,20,40 μmol/L时,K562/G01细胞凋亡率分别为(3.76±1.46)%,(8.89±2.31)%,(18.10±3.56)%,(35.35±3.70)%,差别有统计学意义(n=3,P<0.05);凋亡相关蛋白Bcl-2及procaspase-3的表达下降;组蛋白H3、H4乙酰化及组蛋白H3K4甲基化水平均上升,而H3K9甲基化水平下降,随着作用时间的延长变化趋势更加明显.结论 PHI能诱导K562/G01细胞凋亡,可能与PHI对组蛋白的乙酰化及甲基化调控有关.
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