摘要/Abstract

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


PDF全文下载地址:

点我下载PDF