组蛋白去乙酰化酶抑制剂曲古抑菌素(TSA)对骨肉瘤MG-63的诱导凋亡作用及其机制研究  

Mechanism of Histone Deacetylase Inhibitor Trichostatin A Induced Apoptosis in Human Osteosarcoma Cells MG-63

作　　者：薛小云[1] 吕智[2] 刘小丽[3] 冯毅[3] 贾鹏[1] 

机构地区：[1]山西医科大学临床系,山西太原030001 [2]山西医科大学第二医院骨科,山西太原030001 [3]山西医科大学第二医院病理科,山西太原030001

出　　处：《中国现代医生》2011年第5期7-9,共3页China Modern Doctor

摘　　要：目的探讨组蛋白去乙酰化酶抑制剂(HDACIs)曲古抑菌素(TSA)对骨肉瘤细胞株MG-63的杀伤作用及机制。方法以不同浓度的TSA作用于体外培养的骨肉瘤细胞,采用MTT法检测细胞生长抑制率;以流式细胞技术(FCM)测不同浓度TSA作用前后骨肉瘤细胞周期变化情况;免疫细胞化学技术观察对Survivin基因和血管内皮生长因子(VEGF)的表达水平;RT-PCR分析TSA作用前后骨肉瘤细胞内P21waf1/cip1mRNA的表达变化。结果 TSA在纳摩尔浓度即可抑制细胞增殖;FCM检测到细胞周期发生改变,G2/M期细胞较对照组增多。免疫组化结果表明,该药能明显抑制Survivin和VEGF蛋白的表达,RT-PCR结果表示TSA能显著诱导P21waf1/cip1mRNA表达。上述结果都有明显的量-效关系。结论 TSA作用于G2/M期并有效诱导体外培养的骨肉瘤细胞凋亡,其诱导凋亡机制之一可能是通过抑制Survivin和VEGF基因的表达并且上调P21蛋白水平实现的。Objective To explore the apoptosis mechanism of MG-63 cell induced by TSA. Methods The MTT method was used to test MG-63 cell growth.The cell cycle were test by FCM.Immunochemistry were used to observe the expression of survivin gene and VEGF in MG-63 cell line after treated by TSA. Semi-quantitative RT-PCR was used to detect the mRNA expressions of P21waf1/cip1. Results MG-63 cell were very sensitive to TSA which inhibited the growth of cell in a concentrantion-dependent manner. Flow cytometry data indicated that the increases in the G2/M phase cell percentage and concomitant fall in the percentage of G0/G1 phase cells. By increasing the TSA concentration,the expression of survivin and VEGF decreased gradually. After be treated 24h by TSA, the express of P21waf1/cip1 mRNA was increased in MG-63 cell. Conclusion TSA effect the activity of cyclin-dependent kinase through increase the express of P21waf1/cip1 mRNA.TSA make MG-63 cells blockage G2/M phase and inhibit cell proliferation of MG-63 cells.

关 键 词：凋亡 曲古抑菌素 骨肉瘤细胞 细胞周期 

分 类 号：R737.31[医药卫生—肿瘤]