中文摘要：

目的观察曲古抑菌素A（TSA）对脑胶质瘤细胞组蛋白H4乙酰化的调节和对NDRG2表达的影响及其对细胞增殖的作用。方法0．1～1．0μmol／LTSA分别处理U251细胞12～96h后用四甲基偶氮唑蓝（MTr）法比色检测U251细胞的生长活性，流式细胞仪（FCM）分析细胞周期，实时定量多聚酶链反应（real—timePCR）检测U251细胞NDRG2的mRNA表达水平，Westernblot方法检测组蛋白H4乙酰化和NDRG2蛋白的表达水平。结果TSA可明显抑制U251细胞的增殖；流式细胞仪检测显示G0／G1期细胞比例增加，S期细胞比例略有降低，表明发生G0／G1阻滞，随用药剂量的增加还伴有明显的G2／M阻滞。加入不同浓度TSA后，NDRG2的mRNA和蛋白表达水平明显增高，组蛋白H4的乙酰化水平也明显增强。结论一定浓度的TSA可抑制U251细胞的增殖，提高组蛋白H4乙酰化及NDRG2的表达水平，这可能是其抗肿瘤作用机制之一。

英文摘要：

Objective To observe the regulation of histone H4 acetylation and the expression of NDRG2 by trichostatin A （TSA） in U251 cells and the effect of TSA on cell proliferation. Methods U251 cells were treated with 0. 1 - 1.0 μmol/L TSA for 12 - 96 h and the growth activity of U251 cells was measured by methyl thiazolyl tetrazoiran assay （MTT）. Flow eytometry was adopted to analyze cell cycle, and real-time polymerase chain reaction （real-time PCR） was used to detect the expression level of NDRG2 mRNA on U251 cells with various concentrations of TSA in 24 h. The levels of acetylated histone H4 and expression of NDRG2 protein were checked by Western blot. Results U251 cell proliferation was significantly inhibited by TSA. The proportion of cells in G1/G0 phase increased apparently, while that of cells in S phase reduced slightly; most of cells were arrested in G1/G0 phase after drug treatment and the arrest in G2/M phase was also evident with the increase of the concentration of TSA. The mRNA and protein level of NDRG2 were increased markedly and histone H4 acetylation was obviously enhanced after TSA treatment. Condttsion TSA can significantly inhibit the proliferation of U251 cells and increase the histone acetylation and expression of NDRG2, which probably is the important antineoplastic mechanism.