曲古抑菌素A对肾癌细胞系GRC-1生长的抑制作用

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.

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

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 bcl-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.