TSA抑制人胰腺癌PANC1细胞生长的实验研究  

Trichostatin A(TSA) suppresses the growth of pancreatic adenocarcinoma cells

作　　者：汪理[1] 周伟[1] 张景辉[1] 刘涛[1] 王春友[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胰腺外科中心,湖北武汉430022

出　　处：《中国普通外科杂志》2010年第3期234-238,共5页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(30801098)

摘　　要：目的研究去乙酰化转移酶抑制剂TSA对人胰腺癌PANC-1细胞生长的影响及其作用机制。方法用不同浓度的TSA处理PANC-1细胞。MTT法检测肿瘤细胞的增殖;流式细胞仪分析细胞凋亡及细胞周期;Western免疫印迹及荧光定量RT-PCR分析抗凋亡基因bcl-2和肿瘤抑制基因p21WAF1/CIP1的表达。结果TSA作用于PANC-1细胞能明显抑制细胞的增殖,且具有明显的剂量依赖性;TSA处理72 h的PANC-1细胞其早期凋亡率明显提高(P<0.05),G0/G1期细胞比例显著升高(P<0.05),S期细胞比例显著降低(P<0.05)。TSA在转录和翻译水平上能明显下调bcl-2的表达(P<0.05),上调p21WAF1/CIP1的表达(P<0.05)。结论TSA可以通过诱导胰腺癌细胞的凋亡和周期阻滞而抑制癌细胞生长;其发生机制可能与下调抗凋亡基因bcl-2和上调肿瘤抑制基因p21WAF1/CIP1的表达有关。Objective To investigate the effects of histone deacetylase inhibitor trichostatin A（TSA）,on the cell growth of human pancreatic cancer cell line PANC-1 in vitro and its mechanism.Methods The proliferating activity of PANC-1 cells was observed by MTT assay.The cell apoptosis and cell cycle distribution were detected by flow cytometry.Western blot and real-time PCR were used to assess the expression levels of inhibitor of apoptosis gene bcl-2 and cell cycle regulation gene p21WAF1/CIP1.Results A dose dependent inhibition was remarkably confirmed in PANC-1 cells treated by TSA.As compared with control group,apoptosis rate of PANC-1 cells in TSA group was increased obviously at 72h（P 0.05）.The percentage of G0/G1 phase increased markedly,while the percentage of S phase decreased significantly（P 0.05）.Furthermore,the expression level of bcl-2 mRNA and protein in TSA group was significantly lower than that in control group（P 0.05）.The expression level of p21WAF1/CIP1 mRNA and protein in TSA group was significantly higher than that in control group（P 0.05）.Conclusions Our data demonstrate that TSA-induced growth arrest of pancreatic cancer cell line is induced by a block in the G0/G1 phase and apoptosis,which may occur through down-regulated expression of apoptosis gene bcl-2 and up-regulated expression of cell cycle regulation gene p21WAF1/CIP1.

关 键 词：胰腺肿瘤 组蛋白酶乙酰化酶抑制剂 bcl-2 P21WAF1/CIP1 

分 类 号：R735.9[医药卫生—肿瘤]