曲古抑菌素A对肾癌细胞系GRC-1生长的抑制作用  

Inhibitory Effects of Trichostatin A on Human Renal Carcinoma Cell Line GRC-1

作　　者：王涛[1] 罗浩[2] 秦前波[3] 

机构地区：[1]武汉科技大学医学院人体解剖教研室,430065 [2]华中科技大学同济医学院校医院,武汉430030 [3]武汉大学中南医院普外科,430071

出　　处：《医药导报》2012年第1期11-14,共4页Herald of Medicine

摘　　要：目的研究组蛋白去乙酰化酶(HDAC)抑制药曲古抑菌素A(TSA)对肾癌GRC-1细胞生长的影响及其作用机制。方法使用TSA处理GRC-1细胞。噻唑蓝(MTT)法检测细胞生长;流式细胞仪分析细胞凋亡及细胞周期;Western blot免疫印迹分析p53,p21和bcl-2表达。结果 TSA能明显抑制GRC-1细胞的增殖,且具有明显的剂量依赖性;TSA处理72 h的GRC-1细胞早期凋亡率明显提高,G0/G1期细胞比例显著升高,S期细胞比例显著降低。TSA能够明显下调bcl-2的表达,上调p21的表达,而对p53的没有显著影响。结论 TSA可以通过诱导肾肿瘤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p21的表达有关,TSA可能依赖非p53途径调控p21的表达。Objective To investigate the influence of histone deacetylase inhibitor （trichostatin A, .TSA ） on the human renal cancer line GRC-1 and its mechanism. Methods The proliferating activity of GRC-1 by TSA was observed by MTT assay. The cell apoptosis and cell cycle distribution were detected with Flow cytometry. Western blot was used to assess the expression levels of apoptosis gene bel-2 and cell cycle regulation gene p21. Results A dose dependent inhibition was remarkably confirmed in GRC-1 cells treated with TSA. As compared with that in the control group, apoptosis rate of GRC-1 cells in TSA group was increased obviously （ P〈0.05 ）. The percentage of G0/G1 phase increased markedly, while the percentage of S phase decreased significantly by TSA （ P 〈 0. 05 ）. Furthermore, the expression level of bcl-2 protein in TSA group was significantly lower, while p21 protein was significantly higher than those in the control group （P〈0.05）. However, the expression level of p53 protein in TSA group shows no significant difference from that in the control group （ P〉0.05 ）. Conclusion The data demonstrate that TSA induce growth arrest by G0/G1 phase blocking, and apoptosis eliciting, the mechanism of which may occur through down-regulating the expression of apoptosis gene bcl-2 and up-regulating cell cycle regulation gene p21.

关 键 词：曲古抑菌素A 组蛋白酶乙酰化酶抑制药 GRC-1 bcl-2 p53 P21 

分 类 号：R965[医药卫生—药理学]