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.
作者
洪西
刘利杰
黄先玉
罗静
俞建军
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)
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
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）~~
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
histone crotonylation
prostate cancer
bromodomain-containing protein 4 (BRD4)
inhibitor
proliferation
migration
