Zhu Yi-Fang, Ye Bao-Guo, Shen Jian-Zhen, Lin Cong-Meng, Lin Fu-An, Shen Song-Fei, Xu Cheng-Bo
Department of Hematology, The Zhangzhou Municipal Hospital, Fujian Medical University, Zhangzhou 363000, Fujian Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Jun;18(3):638-41.
This study was aimed to investigate the effects of sodium valproate (VPA) on the proliferation and regulation of histone acetylation of multiple myeloma cell line U266. U266 cells were treated with VPA. Cell proliferation was determined by CCK-8 assay, and cell cycle were analyzed by flow cytometry (FCM). The expression level of HDAC1 mRNA was detected by RT-PCR, and the protein levels of HDAC1 and histone H3, H4 acetylation was detected by Western blot. The results showed that the VPA inhibited the proliferation of U266 cells in concentration-and time-dependent manners.After exposure to different concentrations of VPA for 48 hours, the proportion of G(0)/G(1) cells increased, while the proportion of S phase cells decreased. The cell cycle was arrested obviously in G(0)/G(1) phase (p < 0.05). The expression of HDAC1 mRNA was inhibited, and the protein level of HDAC1 was down-regulated, while the histone H3/H4 acetylation was up-regulated in U266 cells. It is concluded that the VPA can inhibit cell proliferation of U266 and induce G(0)/G(1) phase arrest. The increase of histone H3/H4 acetylation resulting from inhibiting HDAC1 by VPA might be considered as a possible mechanism.
本研究旨在探讨丙戊酸钠(VPA)对多发性骨髓瘤细胞系U266增殖及组蛋白乙酰化调控的影响。用VPA处理U266细胞。采用CCK - 8法检测细胞增殖,通过流式细胞术(FCM)分析细胞周期。用RT - PCR检测HDAC1 mRNA表达水平,用蛋白质印迹法检测HDAC1蛋白水平及组蛋白H3、H4乙酰化水平。结果显示,VPA以浓度和时间依赖性方式抑制U266细胞增殖。在不同浓度VPA作用48小时后,G(0)/G(1)期细胞比例增加,而S期细胞比例降低。细胞周期明显阻滞于G(0)/G(1)期(p < 0.05)。U266细胞中HDAC1 mRNA表达受抑制,HDAC1蛋白水平下调,而组蛋白H3/H4乙酰化上调。结论:VPA可抑制U266细胞增殖并诱导G(0)/G(1)期阻滞。VPA通过抑制HDAC1导致组蛋白H3/H4乙酰化增加可能是其作用机制之一。