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西达本胺对人B淋巴瘤细胞系的作用及其机制

[Effect of chidamide on human B lymphoma cell lines and its mechanisms].

作者信息

Li Yan-Ying, Wang Yan-Fang, Wang Jing, Ke Xiao-Yan

机构信息

Department of Hematology, Peking University Third Hospital, Beijing, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012 Aug;20(4):893-9.

Abstract

This study was aimed to explore the effects of histone deacetylase inhibitor chidamide on the proliferation, apoptosis of B lymphoma cell lines Raji (Burkitt lymphoma), Maver and Z-138 (mantle cell lymphoma) and its mechanisms. Three B lymphoma cell lines were cultured in vitro with different concentrations of chidamide for different time. The cell proliferation was determined by CCK-8 method; the cell apoptosis and mitochondrial membrane potential were analyzed by flow cytometry; the protein levels of histone H3/H4 acetylation in cells and the activity of caspase-3 were detected by Western blot. The results showed that chidamide inhibited the proliferation of 3 B lymphoma cell lines in time- and concentration-dependent manners, especially in Z-138 cell line earlier and faster; chidamide could induce cell apoptosis and decline of mitochondrial membrane potential, which was more sensitive in Maver and Z-138 cells than that in Raji cells. Chidamide could elevate the histone H3/H4 acetylation level in 3 B lymphoma cell lines and the activity of caspase-3 in Maver and Z-138 cells. It is concluded that chidamide can inhibit proliferation of B lymphoma cell lines and promote cell apoptosis, the increase of histone H3/H4 acetylation induced by chidamide, triggering of mitochondrial pathway and activation of caspase-3 may be considered as possible mechanisms.

摘要

本研究旨在探讨组蛋白去乙酰化酶抑制剂西达本胺对B淋巴瘤细胞系Raji(伯基特淋巴瘤)、Maver和Z - 138(套细胞淋巴瘤)增殖、凋亡的影响及其机制。将三种B淋巴瘤细胞系在体外分别用不同浓度的西达本胺培养不同时间。采用CCK - 8法检测细胞增殖;通过流式细胞术分析细胞凋亡和线粒体膜电位;用蛋白质免疫印迹法检测细胞中组蛋白H3/H4乙酰化水平及半胱天冬酶 - 3的活性。结果显示,西达本胺以时间和浓度依赖性方式抑制3种B淋巴瘤细胞系的增殖,在Z - 138细胞系中作用更早且更快;西达本胺可诱导细胞凋亡及线粒体膜电位下降,在Maver和Z - 138细胞中比在Raji细胞中更敏感。西达本胺可提高3种B淋巴瘤细胞系中组蛋白H3/H4乙酰化水平以及Maver和Z - 138细胞中半胱天冬酶 - 3的活性。结论是,西达本胺可抑制B淋巴瘤细胞系的增殖并促进细胞凋亡,西达本胺诱导的组蛋白H3/H4乙酰化增加、线粒体途径的触发及半胱天冬酶 - 3的激活可能是其作用机制。

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