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西达本胺联合顺铂对三阴乳腺癌细胞株 MDA-MB-231的体外抗增殖作用及其机制的研究
作者:项丹1 2  姜藻1  顾晓怡1 
单位:1. 东南大学附属中大医院 肿瘤中心, 江苏 南京 210009;
2. 东南大学环境医学工程 教育部重点实验室, 江苏 南京 210009
关键词:三阴乳腺癌 西达本胺 顺铂 组蛋白脱乙酰基酶类 基因 ERCC1 
分类号:R737.9;R979.1
出版年·卷·期(页码):2013·32·第三期(283-288)
摘要:

目的:探讨西达本胺联合顺铂对三阴乳腺癌细胞株MDA-MB-231的抑制作用及其可能的分子机制。方法:单独及联合给药后采用MTT法测定MDA-MB-231细胞的增殖,流式细胞仪(FCM)检测细胞凋亡率,Western blotting法分析乙酰化组蛋白H3及HDAC3的表达水平,荧光定量PCR检测ERCC1表达水平。结果:MTT法检测发现,西达本胺单药和顺铂单药在体外对细胞株MDA-MB-231增殖都有一定的抑制作用,且呈浓度、时间依赖性;联合用药可起到协同效应。西达本胺可抑制MDA-MB-231细胞株HDAC3的表达,提高组蛋白H3的乙酰化水平。联合顺铂起到协同效应的分子机制主要是降低细胞株ERCC1的表达水平。结论:西达本胺联合顺铂在体外能协同抑制三阴乳腺癌细胞株MDA-MB-231的增殖。

Objective: To explore the chidamide in combination with cisplatin on three negative breast cancer cells MDA-MB-231 inhibition and its possible molecular mechanism. Methods: The separate and combined administration with MTT method for the determination of MDA-MB-231 cell proliferation,flow cytometry(FCM) examination apoptosis rate,analysis of Western blotting acetylation of histone H3 and HDAC3 expression levels,fluorescence quantitative PCR detection of ERCCl expression level. Results: The detection of MTT showed that chidamide monotherapy and cisplatin monotherapy for in vitro cell line MDA-MB-231 value has certain inhibitory action in a dose-and time-dependent manner.Combined medication can play a synergistic effect.Chidamide can inhibit MDA-MB-231 cell HDAC3 expression,increased histone H3 acetylation levels. The synergistic effect combined with cisplatin of molecular mechanism is to decrease the expression of ERCC1. Conclusion: Chidamide in combination with cisplatin in vitro may synergistically inhibit the proliferation of TNBC cell lines MDA-MB-231.

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