组蛋白去乙酰化酶抑制剂对骨肉瘤侵袭性及HIF-1α表达的影响  

The effect of histone deacetylase inhibitor on invasion and expression of HIF-1α in osteosarcoma

作　　者：杨庆诚[1] 曾炳芳[1] 施忠民[1] 张智长[1] 

机构地区：[1]上海交通大学附属第六人民医院骨科,上海200233

出　　处：《肿瘤》2008年第6期472-475,共4页Tumor

基　　金：上海交通大学医学院博士点基金项目(编号:BXJ0631)

摘　　要：目的:探讨组蛋白去乙酰化酶(histone deacetylase,HDAC)抑制剂体外抗骨肉瘤活性及作用机制。方法:体外去铁胺模拟低氧培养骨肉瘤MG-63细胞株,给予曲古抑霉素A(trichostatin A,TSA)处理,Transwell法检测TSA对骨肉瘤细胞侵袭性的影响,RT-PCR、Western印迹法、ELISA等方法检测TSA在不同浓度、不同作用时间点时对骨肉瘤MG-63细胞HIF-1α及VEGF mRNA、蛋白表达的影响。结果:骨肉瘤MG-63细胞经TSA50、100、200、300和500 nmol/L处理后,细胞侵袭性明显降低,与对照组比较差异有统计学意义(P<0.05);模拟低氧可以诱导HIF-1α及VEGF mRNA、蛋白的表达,TSA明显抑制HIF-1α及VEGF的表达,并呈一定的量效及时效关系。结论:HDAC抑制剂具有明显的体外抗骨肉瘤活性,抑制HIF-1α的表达及抗血管生成,可作为一种通过HIF-1α靶点发挥抗血管生成作用的新型抗瘤药物。Objective ： To investigate the anticancer activity of histone deacetylase（HDAC） inhibitor trichostatin A （TSA） on osteosarcoma in vitro and its possible mechanism, nethods：Osteosarcoma MG-63 cells were cultured under the mimic hypoxia condition induced by desferrioxamine and treated with TSA in vitro. The effects of TSA on invasion of MG-63 cells was detected by Transwell migration assay. The effect of TSA on mRNA and protein expressions of HIF-1α and VEGF were tested by RT-PCR, Western blotting, and ELISA at various concentrations and different time points. Results：After treatment with TSA at 50, 100,200,300, and 500 nmol/L the invasion capability of MG-63 cells decreased significantly compared with the control group （ P 〈0.05 ）. Mimic hypoxia induced the ex- pression of HIF-1α and VEGF protein. TSA markedly inhibited the expression of HIF-1α and VEGF protein in a dose- and time-depend- ent manner. Conclusion ：The histone deacetylase inhibitor TSA had an significant anticancer activity in vitro and inhibitory effects on the expression of HIF-1α and tumor angiogenesis. It might be a novel anti-cancer agent by targeting HIF-1α and subsequently inhibiting angiogenesis in osteosarcoma.

关 键 词：骨肉瘤 肿瘤浸润 曲古抑霉素A 缺氧诱导因子1 1α亚基 

分 类 号：R738.1[医药卫生—肿瘤]