上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2019, Vol. 39 ›› Issue (7): 721-.doi: 10.3969/j.issn.1674-8115.2019.07.006

• 论著·基础研究 • 上一篇    下一篇

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

洪西 1，刘利杰 1，黄先玉 2，罗静 2，俞建军 1   

  1. 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
  • 出版日期:2019-07-28 发布日期:2019-08-26
  • 作者简介:洪西（1992—），男，硕士生；电子信箱： 851876614@qq.com。
  • 基金资助:
    上海市科学技术委员会“一带一路”项目（17410742300）

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

HONG Xi1, LIU Li-jie1, HUANG Xian-yu2, LUO Jing2, YU Jian-jun1   

  1. 1. Department of Urology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China; 2. Academy of Life Sciences, East China Normal University, Shanghai 200241, China
  • Online:2019-07-28 Published:2019-08-26
  • Supported by:
    “the Belt and Road” Project of Shanghai Science and Technology Commission, 17410742300

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摘要： 目的 ·探讨溴结构域蛋白 4（bromodomain-containing protein 4，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。

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

Abstract:

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 were detectedWestern 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 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 inhibitedI-BET762. Conclusion · In prostate cancer cells, I-BET762 can reduce the histone crotonylation and also inhibit cell proliferation and migration.

Key words: histone crotonylation, prostate cancer, bromodomain-containing protein 4 (BRD4), inhibitor, proliferation, migration

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