溴结构域蛋白4抑制剂对前列腺癌细胞组蛋白巴豆酰化修饰以及增殖、迁移的影响  

Effects of BRD4 inhibitor on histone crotonylation, proliferation and migration of prostate cancer cells

作　　者：洪西 刘利杰[1] 黄先玉 罗静 俞建军[1] HONG Xi;LIU Li-jie;HUANG Xian-yu;LUO Jing;YU Jian-jun(Department of Urology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University,Shanghai 200233,China;Academy of Life Sciences,East China Normal University, Shanghai 200241,China)

机构地区：[1]上海交通大学附属第六人民医院泌尿外科,上海200233 [2]华东师范大学生命科学院,上海200241

出　　处：《上海交通大学学报（医学版）》2019年第7期721-729,共9页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科学技术委员会“一带一路”项目（17410742300）~~

摘　　要：目的·探讨溴结构域蛋白4(bromodomain-containing protein4,BRD4)抑制剂I-BET762对前列腺癌细胞组蛋白巴豆酰化修饰以及前列腺癌细胞增殖、迁移的影响。方法·选取3种人前列腺癌细胞系LNCaP、C4-2B和PC-3,分别以各自的半数抑制浓度的I-BET762处理,Western blotting检测组蛋白上巴豆酰化修饰以及乙酰化酶的表达。CCK-8、Transwell迁移实验和划痕实验分别测定I-BET762对于LNCaP、C4-2B和PC-3细胞的增殖、迁移的影响。结果·I-BET762可以抑制组蛋白乙酰化酶P300和GCN5的表达,降低组蛋白巴豆酰化修饰表达。Transwell迁移实验和划痕实验结果表明,I-BET762可以抑制前列腺癌细胞系LNCaP、C4-2B和PC-3的迁移能力(均P<0.01);CCK-8实验结果表明,I-BET762处理后,3种前列腺癌细胞系的增殖能力被抑制。结论·前列腺癌细胞中I-BET762能够降低组蛋白巴豆酰化修饰水平,抑制细胞增殖和迁移。Objective · To investigate the effects of bromodomain-containing protein 4 (BRD4) inhibitor I-BET762 on histone crotonylation, proliferation and migration of prostate cancer cells. Methods · Three human prostate cancer cell lines, i.e., LNCaP, C4-2B and PC-3, were respectively treated with I-BET762 of half maximal inhibitory concentration. Histone crotonylation modification and acetylase expression were detected by Western blotting. CCK-8, transwell migration test and scratch test were used to detect the effects of I-BET762 on proliferation and migration of LNCaP, C4-2B and PC-3 cells. Results · I-BET762 inhibited the expression of histone acetylase P300 and GCN5, and reduced the histone crotonylation modification. Transwell migration test and scratch test showed that I-BET762 could inhibit the migration of prostate cancer cell lines LNCaP, C4-2B and PC-3 (all P<0.01);CCK-8 test showed that the proliferation of three prostate cancer cell lines was inhibited by I-BET762. Conclusion · In prostate cancer cells, I-BET762 can reduce the histone crotonylation and also inhibit cell proliferation and migration.

关 键 词：组蛋白巴豆酰化修饰 前列腺癌 溴结构域蛋白4 抑制剂 增殖 迁移 

分 类 号：R737.25[医药卫生—肿瘤]