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TSA诱导胰腺癌BxPC-3细胞周期阻滞与凋亡的研究 预览 被引量:1

Induction of cell cycle arrest and apoptosis in BxPO-3 human pancreatic cancer cells by trichostatin A
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摘要 目的观察曲古抑菌素A(tricho-statin A,TSA)对胰腺癌BxPC-3细胞增殖及凋亡的诱导作用,探讨TSA抗胰腺癌的作用机制。方法BxPC-3细胞应用TSA处理后采用流式细胞技术分析其细胞周期分布和细胞凋亡率,免疫组化方法检测细胞乙酰化组蛋白H4表达,Western blot分析p21 WAF1/CIP1蛋白表达。结果TSA对胰腺癌BxPC-3细胞具有生长抑制作用,且呈时间和剂量依赖性。TSA可将BxPC-3细胞阻滞于G0/G1期,TSA组G0/G1期细胞达(61.8±2.5)%,较空白对照组(42.5±2.2)%和乙醇对照组(47.3±3.4)%明显增多(P=0.004);三组细胞凋亡率分别为25.5%、5.5%和5.1%(P=0.000)。TSA组细胞p21 WAF1/CIP1蛋白表达及其相关染色质乙酰化组蛋白H4表达上调。结论TSA对胰腺癌BxPC-3细胞增殖和细胞周期具有影响作用并可诱导细胞凋亡,p21 WAF1/CIP1蛋白及其相关染色质乙酰化组蛋白H4表达上调可能是其抗胰腺癌作用机制之一。 OBJECTIVE:To investigate the effect and its mechanism of trichostatin A(TSA) on inhibition of cell proliferation and induction of apoptosis in BxPC-3 human pancreatic cancer cells. METHODS:A human pancreatic cancer cell line BxPC-3 was treated with TSA. The cell cycle status and apoptosis were carried out by flow cytometry . Expression of acetylated histone H4 was determined with the immunocytochemical assay.Expression of p21 WAF1/CIP1 was detected by Western blotting. RESULTS:TSA significantly inhibited the proliferation of BxPC-3 human pancreatic cancer cells in a time-and dose-dependent manner. BxPC 3 cells treated with TSA was arrested in G0/G1 phase. Compared with the blank control group (42.5 ± 2.2)% and ethanol group (47.3 ± 3.4)% ,TSA group (61.8 ± 2.5 )% was significantly increased (P= 0. 004). The apoptosis rate of BxPC-3 cell was markedly enhanced in TSA group (25.5%) compared with the blank control group (5.5%) and ethanol group (5. 1%),P=0.000. The expressions of acetylated histone H4, p21 WAF1/CIP1 were significantly increased after being treated with TSA. CONCLUSIONS:The results suggest that TSA may inhibit pancreatic cancer cell growth in vitro, and in duee cell cycle arrest and the apoptosis rate of BxPC 3 human pan creatic cancer cell. TSA acts as an anti cancer agent by up regulating the expressions of acetylated histone H4 and p21 WAF1/CIP1.
作者 张世能 蔡霞 徐凤琴 张亚雷 黄志清 曾志勇 ZHANG Shi-neng , CAI Xia , XU Feng-qin ZHANG Ya lei, HUANG Zhi qing , ZENG Zhi yong (1. Department of Gastroenterology , Second Affiliated Hospital, Sun Yat-sen University ,Guangzhou 510120,P. R. China 2. Affiliated Tumor Hospital, Guangzhou Medical College . Guangzhou 510095, P. R. China)
出处 《中华肿瘤防治杂志》 CAS 2007年第7期 525-528,共4页 Chinese Journal of Cancer Prevention and Treatment
基金 广东省自然科学基金(04009381)
关键词 抗肿瘤药/药理学 胰腺肿瘤/病理学 细胞周期 细胞凋亡/药物作用 免疫组织化学 Antineoplastic agents/pharmacology pancreatic neoplasms/pathology cell cycle apoptosis/drug therapy Immunohistochemlstry
作者简介 [通讯作者简介]张世能,男,安徽庐江人,博士,副教授,硕士生导师,主要从事胰腺癌的基础和临床研究工作。Tel:86-20-81332598 E—mail:shinengz@163.net
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