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-  2015 

溴化结构域蛋白抑制剂JQ1对人乳腺癌细胞的作用 Efficacy of BET Bromodomain Inhibitor JQ1 in Breast Cancer

Keywords: BET家族,BRD4,JQ1,乳腺癌

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Abstract:

目的:研究BET家族小分子抑制剂JQ1对乳腺癌细胞增殖、周期及凋亡的影响及其作用机制。方法:JQ1作用于人乳腺癌细胞MDA-MB-231、MCF-7,采用流式细胞术检测细胞凋亡率及细胞周期的变化,MTT法测定细胞存活曲线,克隆形成法测定细胞抑制率,real-time PCR检测c-MYC的基因表达水平变化。Western blotting方法检测c-MYC及BRD4蛋白表达水平的变化。结果:乳腺癌细胞MDA-MB-231对BRD4抑制剂JQ1敏感,而MCF-7则对JQ1耐受。JQ1可以诱导MDA-MB-231细胞G1期阻滞和凋亡,相同的处理因素作用于MCF-7后,则无明显的细胞周期及凋亡水平的改变。JQ1作用于MDA-MB-231细胞后可以显著下调c-MYC基因及蛋白表达水平,而JQ1作用于耐药的MCF-7后,c-MYC的基因的表达水平升高,而蛋白表达水平无明显改变。结论:BET抑制剂提供了一个潜在的治疗乳腺癌的靶点

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