异硫氰酸苯已酯抑制T细胞白血病Jurkat细胞Wnt／β-catenin信号通路的研究  

Effect of Phenylhexyl Isothiocyanate on Wnt/beta-catenin Signaling Pathway in Jurkat Cell Line

作　　者：林娟[1] 黄轶群 马旭东 

机构地区：[1]福建医科大学附属漳州市医院干部病房 [2]血液科,福建漳州363000

出　　处：《中国实验血液学杂志》2013年第2期361-365,共5页Journal of Experimental Hematology

基　　金：卫生部科学研究基金;福建卫生教育联合攻关计划项目资助(编号wkj2008-2-55);福建医科大学科学研究发展专项基金计划项目(编号FZS08018);漳州市科学研究发展计划项目(编号Z07014)

摘　　要：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20μmol/L;PHI处理3 h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H3K9,7 h时作用更明显;PHI作用3 hβ-catenin表达水平无变化,7 h后Wnt/β-catenin信号转导通路β-catenin及其周期相关基因TCF、c-myc、cyclinD1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。This study was purposed to investigate the effect of phenylhexyl isothiocyanate （PHI） on Wnt/β-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 β-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 ceils in time-and dose-depectdent manners. It s IC50 at 48 h was about 20μmol/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 13-catenin was not changed after exposure to PHI for 3 h, but expression of β-catenin, and its cell cycle-related genes such as TCF, c-myc and cyclinD1 decreased after exposure to PHI for 7 h. It is concluded that PHI regulates acetylation and methylation of histone, inhibits Wnt/β-catenin signal pathway, and is able to induce apoptosis and inhibits growth of Jurkat cells.

关 键 词：异硫氰酸苯己酯 T细胞白血病 Jurkat细胞系 WNT/Β-CATENIN信号转导通路 组蛋白乙酰化 

分 类 号：R733.7[医药卫生—肿瘤]