This study was purposed to investigate the effect of phenylhexyl isothiocyanate (PHI) on Wnt/p-catenin signaling pathway, histone acetylation, histone methylation and cell apoptosis in Jurkat cell line. The viability of Jurkat cells after treatment with PHI was tested by MTT. Apoptotic rate of Jurkat cells was measured by flow cytometry. The levels of Wnt/β-catenin related proteins including p-catenin,TCF,c-myc, and cyclinD1,histone acetylated H3 and H4, histone methylated H3K9 and H3K4 were detected by Western blot. The resuts showed that PHI inhibited the cell growth and induced apoptosis in Jurkat cells in time-and dose-depectdent manners. It s IC50 at 48 h was about 20 μmol/L. Expression of histone acetylated H3, H4 and histone methylated H3k4 increased after exposure to PHI for 3 h, while histone methylated H3K9 decreased. Expression of (S-catenin was not changed after exposure to PHI for 3 h, but expression of p-catenin, and its cell cycle-related genes such as TCF, c-myc and cyclinDl decreased after exposure to PHI for 7 h. It is concluded that PHI regulates acetylation and methylation of histone, inhibits Wnt/p-catenin signal pathway, and is able to induce apoptosis and inhibits growth of Jurkat cells.%本研究目的在于探索研究异硫氰酸苯己酯(PHI)在体外对人类T细胞白血病Jurkat细胞Wnt/β联蛋白(catenin)信号通路及组蛋白调控、细胞凋亡和增殖的影响.用MTT方法检测PHI作用后Jurkat细胞的增殖率变化；用流式细胞术观察细胞凋亡；用Western blot观察Jurkat细胞Wnt/β-catenin信号转导通路相关蛋白β-catenin、TCF、c-myc、cyclinD1水平的变化,以及组蛋白甲基化H3K4,H3K9、乙酰化H3,H4的变化.结果表明,PHI可抑制Jurkat细胞增殖,诱导细胞凋亡,呈浓度和时间依赖性,48 h的IC50约为20 μmol/L; PHI处理3h后上调组蛋白乙酰化H3、H4和组蛋白甲基化H3K4,下调组蛋白甲基化H3K9,7h时作用更明显；PHI作用3 hβ-catenin表达水平无变化,7h后Wnt/β-catenin信号转导通路β-catenin及其周期相关基因TCF、c-myc、cyclinDI表达均下降.结论:PHI抑制Jurkat细胞Wnt/β-catenin信号转导通路,调控组蛋白甲基化、乙酰化,从而诱导细胞凋亡,抑制细胞增殖.
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