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[目的]研究去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACi)西达本胺(Chi-damide,实验室编号:CS055)对结肠癌细胞株LoVo体外生物学特性的影响、诱导细胞凋亡的分子机制。[方法]MTT法观察CS055(2、4、8、16、32、64μmol/L)对LoVo增殖抑制情况,流式细胞仪检测细胞周期阻滞,Westernblot检测p21、CDK4、caspase-3蛋白表达情况。[结果]CS055体外能明显抑制LoVo细胞的增殖,呈剂量、时间依赖性(P<0.05)。CS055(16μmol/L、48h)诱导后,流式细胞仪检测示细胞被阻滞于G0/G1期,并且出现典型的亚二倍体(sub-G1)峰。CS055可明显提高p21、caspase-3蛋白的表达水平,下调CDK4蛋白的表达水平。[结论]CS055可通过诱导细胞周期阻滞及细胞凋亡而发挥体外抗结肠癌LoVo细胞增殖作用,其作用机制可能涉及对p21、CDK4、caspase-3蛋白表达的调控。
[Objective] To investigate the effects of HDACi Chi-damide (CS055) on the biological characteristics of colon cancer cell line LoVo in vitro and to induce apoptosis Molecular mechanism. [Methods] The inhibitory effect of CS055 (2,4,8,16,32,64μmol / L) on the proliferation of LoVo was observed by MTT assay. The cell cycle arrest was detected by flow cytometry. The expressions of p21, CDK4 and caspase-3 protein were detected by Western blot . [Result] CS055 could significantly inhibit the proliferation of LoVo cells in vitro in a dose-and time-dependent manner (P <0.05). After induction with CS055 (16μmol / L, 48h), the cells were arrested in G0 / G1 phase by flow cytometry, and the typical sub-G1 peak appeared. CS055 can significantly improve the expression of p21, caspase-3 protein and down-regulate the expression of CDK4 protein. [Conclusion] CS055 can induce proliferation of LoVo cells in vitro by inducing cell cycle arrest and apoptosis. The mechanism may be related to the regulation of p21, CDK4 and caspase-3 protein expression.