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Bax/Bcl-2表达变化在HDAC抑制因子TSA诱导脑胶质瘤细胞凋亡中的作用机制研究 被引量:3

The role of Bax/Bcl-2 expression in apoptosis of glioma cells induced by HDAC inhibitor TSA
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摘要 目的:探讨HDAC抑制因子TSA对脑胶质瘤U251细胞增殖及凋亡的诱导作用,并分析其作用的分子机制.方法:采用CCK8法检测HDAC抑制因子TSA对U251细胞增殖的影响;U251细胞的凋亡率采用流式细胞仪进行检测;caspase-3、caspase-9、bcl-2和bax mRNA表达水平按照RT-PCR检测试剂盒的说明进行检测.Western blot检测bcl-2和bax蛋白表达.结果:HDAC抑制因子TSA对U251细胞具有明显的增殖抑制作用,并呈现剂量和时间依赖性;药物作用后U251细胞以早期凋亡为主;bcl-2 mRNA表达水平呈下降,bax mRNA表达水平上升,下游活化Caspase-3和Caspase-9基因表达上升;TSA可上调bax蛋白和下调bcl-2蛋白的表达,bcl-2/bax比值降低.结论:HDAC抑制因子TSA主要通过降低bcl-2/bax比值和活化caspase-3/-9诱导U251细胞发生凋亡,该药具有抗脑胶质瘤的潜在应用价值. Objective: To detect the effect of HDAC inhibitor TSA on proliferation and apoptosis of U251 cells and its related mechanisms. Methods: Cell proliferation was analyzed using Cell Counting Kit-8 assay. The level of cell apoptosis was detected by Annexin V-FITC/PI double staining analysis. The mRNA expression of caspase-3, caspase-9, bcl-2 or bax were detected by RT-PCR assay, and Western blot assay was carried out to detect protein expression of Bax and Bcl-2 . Results: TSA inhibited the proliferation of U251 cells in a time-and dose-dependent manner. The Annexin V/PI double staining assay indicated that TSA could induce obvious apoptosis in early stage. The expression of caspase-3, caspase-9 and bax mRNA was obviously up-regulated, while bcl-2 down-regulated, which accordingly consistent with the expression of their proteins. Conclusion: It was indicated that TSA can significantly inhibit the proliferation of U251 cells by inducing apoptosis of U251 cells, which was related to down-regulation of Bcl-2/Bax ratio, and TSA might be a promising drug for gliomas therapy.
作者 周飞 夏伟伟 孙王男 史美燕 齐福 王凤芹 王宪伟 ZHOU Fei;XIA Wei-wei;SUN Wang-nan(College of Medicine and Life Sciences, Jinan University Shandong Academy of Medical Sciences, Shandong Jinan 250062)
出处 《医学检验与临床》 2019年第8期7-10,共4页 Medical Laboratory Science and Clinics
关键词 HDAC抑制因子TSA 增殖 凋亡 U251细胞 HDAC inhibitor TSA Proliferation Apoptosis U251 cells
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