组蛋白去乙酰化酶抑制剂MS-275对U266细胞增殖的影响

Effects of histone deacetylase inhibitor MS-275 in vitro on proliferation of U266 cell line

  • 摘要: 目的 研究组蛋白去乙酰化酶抑制剂MS-275对人多发性骨髓瘤细胞U266增殖的影响。方法 将不同浓度的MS-275以不同时间作用于U266细胞,用台盼蓝拒染法观察药物对细胞活力的影响;瑞氏-姬姆萨染色观察药物对细胞形态学变化;流式细胞仪分析细胞周期;Western Blot检测P21、Cdk4、Acetyl-histone H3及PARP等的蛋白表达。结果 MS-275呈时间和剂量依赖性抑制U266细胞增殖,阻断细胞周期于G0/G1期,细胞发生明显变化。出现P21表达增加,Cdk4表达下降,同时出现PARP的裂解。结论 组蛋白去乙酰化酶抑制剂MS-275具有抑制人骨髓瘤细胞U266增殖作用,使细胞阻滞在G0/G1期,最终诱导U266细胞凋亡。

     

    Abstract: Objective To investigate the antitumor effect of MS-275,a histone deacetylase inhibitor,on growth of the human myeloma cell line U266. Methods Cultured U266 cells were exposed to different concentrations of MS-275 for different periods of time. Cell viability was evaluated by trypan blue exclusion assay and cell count. Cell morphologic changes were observed with Wright-Giemsa staining. Cell cycle was analyzed by flow cytometry,and proteins of poly(ADP-ribose) polymerase(PARP), P21 and Cdk4,were detected by Western blot. Results MS-275 inhibited the growth of U266 cells in a dose-and time-dependent manner. The cell cycle was arrested at G0/G1 phase,and the visible morphological changes in U266 cells were confirmed with Wright-Giemsa staining. Western blot showed cleaved-PARP,increased P21 expression,and down-regulation of Cdk4 expression in MS-275-treated U266 cells. Conclusion MS-275 can inhibit the proliferation of U266 cells,arrest the cell cycle at G0/G1 phase,and induce apoptosis of U266 cells.

     

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