丙戊酸钠对白血病细胞Jurkat的增殖抑制作用  

Inhibition of valproic acid sodium on proliferation of acute T lymphoblastic leukemia cell line Jurkat

作　　者：林聪猛[1] 朱艺芳[1] 叶宝国[1] 沈建箴[2] 林福安[1] 沈松菲[2] 徐成波[2] 陈璐[2] 

机构地区：[1]福建医科大学附属漳州市医院血液科,363000 [2]福建医科大学附属协和医院血研所

出　　处：《白血病．淋巴瘤》2010年第7期412-414,417,共4页Journal of Leukemia & Lymphoma

基　　金：漳州市2006年科技计划项目（Z06079）

摘　　要：目的 探讨丙戊酸钠（VPA）对Jurkat细胞增殖抑制作用及对组蛋白乙酰化修饰调控的影响.方法 采用CCK-8法检测VPA对Jurkat细胞增殖的抑制作用;流式细胞术检测VPA作用前后Jurkat细胞周期的变化情况;半定量RT-PCR检测VPA作用前后Jurkat细胞中组蛋白去乙酰化酶1（HDAC1）mRNA的表达变化;Western blotting检测VPA作用前后HDAC1及组蛋白H3、H4乙酰化蛋白水平的变化.结果 VPA对Jurkat细胞的增殖抑制作用呈时间-浓度依赖性;不同浓度的VPA处理细胞48 h后,细胞周期检测显示随浓度增加,G0/G1期比例增高,S期比例下降,细胞被阻滞在G0/G1期（P〈0.05）;RT-PCR证实VPA能够抑制HDAC1 mRNA水平的表达;Western blotting方法分析证实,不同浓度VPA作用细胞48 h后降低HDAC1蛋白水平,提高组蛋白H3、H4乙酰化表达水平.结论 VPA能抑制Jurkat细胞增殖,阻滞细胞周期于G0/G1期,这可能与VPA抑制HDAC1表达,上调组蛋白H3、H4乙酰化水平有关.Objective To investigate the inhibition of proliferation and the regulation of histone acetylation modification in Jurkat cells treated by sodium valproate（VPA）. Methods Jurkat cells were treated with VPA.Cell proliferation was determined by CCK-8 assay, and cell cycle were analyzed by flow cytometry （FCM）. mRNA of HDAC1 was detected by semi-quantitative RT-PCR, and protein expression of HDAC1 and acetylation of histone H3, H4 was examined by Western blotting. Results VPA inhibited the proliferation of Jurkat cells in concentration-and time-dependent manners. After exposure to VPA in different concentrations for 48h,cell cycle was arrested obviously at G0/G1 phase （P 〈0.05）, and with increasing concentration, the percentage of G0/G1 phase cells was increased and that of S phase were decreased. HDAC1 mRNA expression were inhibited with the increasing concentration of VPA. The protein level of HDAC1 was down-regulated, while acetylation of histone H3、H4 was up-regulated in Jurkat cells by VPA. Conclusion VPA can inhibit proliferation of Jurkat cells and induce G0/G1 phase arrest. The mechanism may be that VPA increase acetylation of histone H3/H4 by inhibiting expressions of HDAC1 gene.

关 键 词：丙戊酸 JURKAT细胞 细胞周期 组蛋白脱乙酰基酶类 

分 类 号：R733.7[医药卫生—肿瘤]