丙戊酸钠逆转组蛋白低乙酰化水平对肝癌细胞侵袭转移的体外实验研究

目的探讨丙戊酸钠(VPA)逆转组蛋白低乙酰化水平对体外培养的人肝癌细胞系SMMC-7721细胞体外侵袭、转移能力的影响及其可能的作用机制。方法流式细胞仪(FCM)分析不同浓度VPA对SMMC-7721细胞凋亡及细胞周期的影响;分别采用划痕试验,Transwell侵袭小室和细胞-基质黏附试验测定细胞体外迁移、侵袭和黏附能力;Western blot观察不同浓度VPA处理后HPA和PCNA蛋白的表达变化。结果 VPA诱导SMMC-7721细胞凋亡,阻滞细胞于G2/M期,抑制细胞增殖。VPA试验组细胞的侵袭、迁移能力以及黏附能力均显著低于对照组(P<0.05)。随浓度和时间增加,VPA能明显降低HPA和PCNA蛋白表达。结论 VPA可通过逆转染色体组蛋白低乙酰化水平,显著抑制肝癌细胞增殖,降低肝癌细胞侵袭、迁移和黏附能力。下调HPA和PCNA表达可能是其发挥作用的主要机制之一。

Effect of reversing low-level histone acetylation with VPA on metastasis of hepatocellular carcinoma in vitro

Objective To investigate the inhibitory effect of sodium valproate on hepatic cancer cell line SMMC-7721 and its action mechanism by reversing low-level of histone acetylation.Methods The cell apoptosis and cell cycle distribution were analyzed by flow cytometry(FCM).The cells’ capacity of invasion,migration and cell-matrix-adhesion in vitro were tested by using Scratch Test,Transwell Migration and Adhesion Assay methods.The expression levels of HPA and PCNA were detected by Western blot.Results Sodium valproate inhibited the proliferation of SMMC-7721 cells in a dose-and time-dependent manner and caused cell cycle arrest at G2/M phase.The cells’ capacities of invasion,migration and cell-matrix-adhesion were significantly lower than those in control group(P<0.05).In the experimental groups,the expression levels of HPA and PCNA protein were down-regulated significantly in a dose-and time-dependent manner.Conclusion Sodium valproate can inhibit the proliferation of SMMC-7721 cells and inhibit the cells’ capacity of invasion,migration and cell-matrix-adhesion.The downregulation of the expression of HPA and PCNA may be one of the possible action mechanisms.