PHI对前列腺癌PC3细胞组蛋白甲基化及乙酰化的调控  

Histone Methylation and Acetylation Modulated by PHI in Prostate Cancer PC3 Cell Line

作　　者：庄志明[1] 黄轶群[1] 马旭东[1] 郑亚才[1] 郑周达[1] 

机构地区：[1]福建医科大学附属漳州市医院泌尿外科,漳州363000

出　　处：《华中科技大学学报（医学版）》2012年第6期665-669,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：卫生部研究基金福建卫生教育联合攻关计划资助项目(No.wkj2008-2-55);福建医科大学科研发展专项基金计划资助项目(No.FZS08016)

摘　　要：目的探讨异硫氰酸苯己酯(PHI)诱导前列腺癌PC3细胞凋亡的分子机制。方法采用MTT方法观察PHI对PC3细胞的生长抑制情况;TUNEL方法检测PHI对PC3细胞凋亡的影响;用蛋白免疫印迹法(Western blot)检测凋亡相关蛋白Bcl-2、Caspase-9、Caspase-3、Mcl-1、Cyt-C、XIAP及组蛋白乙酰化H3、H4,组蛋白甲基化H3K9、H3K4水平的变化。结果①PHI能抑制PC3细胞增殖,IC50为20μmol/L;②PHI通过下调PC3细胞Bcl-2,Caspase-9、Caspase-3、Mcl-1、Cyt-C、XIAP表达,诱导PC3细胞凋亡;③PHI使PC3细胞组蛋白乙酰化H3、H4表达增加,组蛋白甲基化H3K4水平增高,H3K9水平降低。结论 PHI可使组蛋白H3、H4高乙酰化,并调控组蛋白H3K4、H3K9甲基化水平,从而抑制PC3细胞的增殖,诱导其凋亡。PHI是一种潜在抗前列腺癌的新药。Objective To investigate the molecular mechanism of phenyhexyle isothiocyanate（PHI）inducing apoptosis of prostate cancer cell line（PC3）in vitro.Methods The viability of PC3 cells after treatment with PHI was examined by using MTT method.Apoptosis of PC3 cells was measured by using TUNEL assay.The protein expression levels of Bcl-2,Caspase-9,Caspase-3,Mcl-1,Cyt-C,XIAP,histone acetylated H3 and H4,and histone methylated H3K9 and H3K4 were detected by using Western blot.Results ①PHI could inhibit the proliferation of PC3 cells,and IC50 was 20 μmol/L;②PHI could induce apoptosis of PC3 cells by down-regulating the expression of Bcl-2,Caspase-9,Caspase-3,Mcl-1,Cyt-C,and XIAP;③PHI significantly induced an accumulation of histone acetylated H3 and H4,histone methylated H3K4,and decreased methylated H3K9.Conclusion PHI could significantly enhance acetylation of histone H3 and H4,and modulate the methylation of histone H3 lysine 4,resulting in the inhibition of PC3 cells proliferation and induction of PC3 cells apoptois.PHI might be a potential novel anti-prostate cancer agent.

关 键 词：异硫氰酸苯己酯 前列腺癌 细胞凋亡 组蛋白去乙酰化酶抑制剂 组蛋白 乙酰化 甲基化 

分 类 号：R737.25[医药卫生—肿瘤]