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曲古霉素A对肺腺癌细胞株NCI-H1299增殖的抑制作用及其机制 被引量：4

Role of trichostatin A in proliferation of human lung adenocarcinoma cell line NCI-H1299 and its mechanism
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摘要 背景与目的:曲古霉素A(trichostatin A,TSA@是具有组蛋白去乙酰化酶(histone deacetylases,HDAC@强效非竞争性抑制剂,对血液系统肿瘤和实质性肿瘤均有较强的生长抑制作用。本文观察HDACs抑制剂TSA对体外培养的肺腺癌NCI-H1299细胞株的增殖、凋亡和周期以及相关基因表达的影响,并探讨其可能的作用机制。方法:MTT法检测不同浓度(0.1、0.2、0.4、2.0μmol/L@的TSA对人肺腺癌NCI-H1299细胞株体外增殖的影响,流式细胞术检测药物处理后细胞周期及凋亡率的变化;Western blot法检测细胞内组蛋白H4乙酰化水平的变化;Real-time PCR检测NCI-H1299细胞内p21、CyclinB1、Bcl-2和Bax的基因表达。结果:TSA能明显抑制NCI-H1299细胞的体外生长,其抑制作用呈明显的剂量和时间依赖性。TSA诱导后,流式细胞术检测结果显示细胞阻滞于G2/M期,细胞凋亡增加。TSA可明显提高NCI-H1299细胞内组蛋白H4的乙酰化水平,诱导p21和Bax的mRNA表达增加,同时抑制Bcl-2和CyclinB1表达。结论:TSA可通过诱导细胞凋亡及阻滞细胞周期而发挥体外抗肺腺癌细胞生长的作用,其机制可能与组蛋白乙酰化水平的提高以及调控相关基因p21、Bax、Bcl-2和CyclinB1的表达变化有关。 Background and purpose：Trichostatin A（TSA）,an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture,is a potent and specifi c inhibitor of histone deacetylase（HDAC）.This study was aimed to investigate the in？ uence of trichostatin A on the growth of human lung adenocacinoma cells in vitro,and to explore the mechanisms involved.Methods：MTT assay was employed to evaluate the inhibitory effect of TSA（0.1,0.2,0.4 μmol/L）on the growth of human NCI-H1299 cancer cells.The cell cycle distribution and apoptotic ratio were determined by ？ ow cytometry.The acetyl level of histone H4 after TSA treatment was detected by Western blot ;the mRNA level of Bax,Bcl-2,p21 and cyclinB1 was measured by Real-time PCR.Results：TSA inhibited the growth of NCI-H1299 cells in a dose-and time-dependent manner.Flow cytometry showed that the cells were blocked at G2/M phase and cell apoptosis was increased compared to the control.TSA signifi cantly increased the acetyl level of histone H4,induced p21 and Bax expression,and inhibited the expression of cyclin B1 and Bcl-2.Conclusion：TSA inhibits the growth of lung cancer cells in vitro through inducing cell apoptosis and cell cycle arrest,which might be related to its regulatory effects on the acetyl blot of histone and the expression of p21,Bax,Bcl-2 and cyclinB1.
作者 顾红军 武宁 胡海洋 宋晓莲 董宇超 李强
机构地区 第二军医大学附属长海医院呼吸内科 解放军一零零医院急诊科
出处 《中国癌症杂志》 CAS CSCD 北大核心 2009年第10期779-783,共5页 China Oncology
关键词 组蛋白去乙酰化酶 肺肿瘤 曲古霉素A 凋亡 histone deacetylases lung neoplasms trichostatin A apoptosis
分类号 R73-361 [医药卫生—肿瘤]
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参考文献28

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共引文献4

同被引文献29

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引证文献4

二级引证文献11

中国癌症杂志
2009年 第10期

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