曲古菌素A对HDAC1在K562细胞中表达的影响

Effect of Trichostatin A on the expression of HDACI in K562 cells

目的：研究表明组蛋白去乙酰化酶1（histone deacetylase，HDAC1）在多种肿瘤中高表达，曲古菌素A（TSA）可以抑制肿瘤细胞的生长。本实验研究HDAC1在K562细胞的表达及TSA对其增殖的影响。方法：100～400nmol／L的TSA分别处理K562细胞6～48h后用四甲基偶氮唑蓝（MTT法）比色检测K562细胞的生长活性；应用流式细胞仪法观察细胞凋亡。采用RT—PCR和蛋白印迹法（Western blot）方法检测K562细胞在（24h）不同浓度（50～500nmlo／L）HDAC1 mRNA和蛋白的表达以及TSA对其作用。结果：TSA可显著抑制K562细胞的生长，可呈时间及剂量依赖性抑制K562细胞的增殖，抑制率为23．15％-76．63％。流式细胞仪检测Raji细胞，凋亡率为10．32％～60．16％。HDAC1的mRNAA值的半定量表达以及蛋白表达明显增强（P〈0．05），但随着浓度的增加而表达下调，呈剂量依赖性下调。结论：TSA对K562细胞具有明显的增生抑制及诱导凋亡作用，抑制HDAC1的表达可能是其重要作用机制之一。

Objective： Histone deacetylase（ HDAC1 ）shows a high expression in many cancer cells and TSA can inhibit it the growth of cancer cells. This paper was designed to investigate the expression of HDAC1 of K562 cell and the effect of TSA on their proliferation and apoptosis. Methods： K562 cells were treated with 100 -400nmol/L TSA for 6 -48h and the growth inhibition rates of K562 cells were measured by MTT. The expression of HDAClon K562 cell were checked by mRNA, Westem blot at 24h various concertrations （50 -500nom/L）. Results： TSA in selectively inhibite proliferation of K562 cell line in a dose and time dependent manner. Inhibit rate was 23.15% - 76.63% （P 〈 0.01 ）. of K562 cells The apoptosis rates were 14.38 -61.18% by flow cytometery （FCM） , the up regulation of HDAC1 expression was observed within 24h after the treatment in TSA by RT - PCR and Western blot. with the increase of concertration and the expression down regulation dose dependent. Conclusion： The expression of HDAC1 plays an important role in the proliferation and apoptosis of K562 cells, which is the inhibition effect of various concentration of TSA on K562 cells.