论著·基础研究

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
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  • 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
洪西(1992—),男,硕士生;电子信箱: 851876614@qq.com。

网络出版日期: 2019-08-26

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
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  • 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 published: 2019-08-26

Supported by

“the Belt and Road” Project of Shanghai Science and Technology Commission, 17410742300

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。

本文引用格式

洪西 1 , 刘利杰 1 , 黄先玉 2 , 罗静 2 , 俞建军 1 . 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[J]. 上海交通大学学报(医学版), 2019 , 39(7) : 721 . DOI: 10.3969/j.issn.1674-8115.2019.07.006

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.
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