异硫氰酸苯己酯对SMMC-7721细胞甲基化和乙酰化组蛋白表达及细胞生长和凋亡的影响

Phenylhexyl isothiocyanate（PHI） regulates histone methylation and acetylation and induces apoptosis in SMMC-7721 cells

目的研究异硫氰酸苯己酯（PHI）在体外对原发性肝癌细胞株SMMC-7721细胞的作用，观察PHI对SMMC-7721细胞甲基化和乙酰化组蛋白表达及细胞生长和凋亡的影响。方法采用锥虫蓝拒染直接计数法观察PHI对SMMC-7721细胞增殖的影响；原位末端标记法观察PHI对SMMC7721细胞凋亡的作用；用Westernblot方法观察PHI作用后SMMC-7721细胞组蛋白H3K4、H3K9甲基化及组蛋白H3、H4乙酰化状态的改变。计量资料实验数据以均数±标准差（x-±s）表示，进行单因素方差分析。结果PHI处理后的细胞增殖受抑制；0、10、20、40μmol／LPHI处理7h后，细胞凋亡率分别为4．50％±2．33％、6．85％±2．43％、17．50％±4．15％、54．50％±3．41％，差异有统计学意义（F=34．22，D〈0．05）；PHI显著提高组蛋白乙酰化H3、H4及甲基化H3K4水平，抑制组蛋白甲基化H3K9表达。结论PHI可能是一种组蛋白去乙酰化酶抑制剂，同时能调控组蛋白甲基化，影响其表观遗传学特性，可能作为新的抗癌药物。

Objective To investigate the effects of PHI on histone acetylation and methylation in hepatocellular carcinoma line SMMC-7721 cells. Methods Apoptosis was measured by TUNNEL assay. Histone methylation and acetylation were detected by Western blot. Results PHI inhibited cells growth and induced apoptosis. PHI treatment resulted in increased acetylation of histone H3 and H4, elevated level of histone H3 lysine 4 methylation, and decreased level of histone H3 lysine 9 methylation. Conclusions PHI can modulate both histone acetylation and methylation, which could remodel chromatin structure. PHI may be a novel anticancer drug.