曲古抑菌素A体内外杀伤卵巢癌细胞  

In vivo and in vitro killing effect of the TSA on ovarian cancell cells

作　　者：张美花[1,2] 金海丹[1] 朴俊杰[1] 林贞花[1,3] 金铁峰[1,3] 

机构地区：[1]延边大学医学院病理学教研室,吉林延吉133000 [2]延边妇幼医院B超室,吉林延吉133000 [3]延边大学肿瘤研究中心,吉林延吉133002

出　　处：《基础医学与临床》2013年第9期1129-1134,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(30960120);吉林省科技厅社会发展重点项目(20090442);吉林省教育厅"十二五"科学技术研究项目(201110)

摘　　要：目的探讨组蛋白去乙酰化酶(HDAC)抑制剂曲古抑菌素A(TSA)在卵巢癌靶向治疗中的作用及机制。方法以2种正常卵巢上皮细胞系IOSE-29和IOSE-329及3种卵巢癌细胞系ES-2、SKOV-3和OVCAR-8为研究对象,应用XTT法和流式细胞术检测TSA对卵巢癌细胞的抗增殖及诱导凋亡作用,并观察其体内疗效。结果对比正常卵巢上皮,卵巢癌及其细胞系中HDAC6蛋白呈强阳性表达,其抑制剂TSA对ES-2,SKOV-3和OVCAR-8卵巢癌细胞系有明显杀伤作用,但正常卵巢上皮细胞对TSA不敏感,TSA处理组的卵巢癌细胞凋亡率和死亡率较未处理组高。体内实验表明:TSA处理组的ES-2裸鼠体内移植瘤生长速度较未处理组慢。结论 TSA可在体内外有效杀伤卵巢癌细胞,其机制部分是通过抑制HDAC6而实现的。Objective To investigate the ovarian cancer killing effect and mechanism of histone deacetylase inhibitor of trichostatin A （TSA）. Methods The ovarian cancers killing effect of TSA was detected by using XTF and flow cytometry technique on two of the normal ovarian epithelial cell lines, IOSE-29 and IOSE-329, and three of the ovarian cancer cell lines, ES-2, SKOV-3, and OVCAR-8. The in vivo effect was also observed. Results HDAC6 protein showed higher positivity in ovarian cancer and its cell lines than in normal ovarian epithelia. ES-2, SKOV-3, and OVCAR-8 ovarian cancer cells were more sensitive for HDACs inhibitor, TSA, treatment as compared with normal ovarian epithelial cell lines （ P 〈 0. 05 ）. Also, the ratio of apoptosis and cell death rate were significantly higher in TSA treated ovarian cancer cells than it in the untreated group. In vivo experiments also showed that ES-2 xenografi treated by TSA was growing much slower compared with untreated ES-2 xenograft. Conclusions TSA may effectively kill the ovarian cancer cells in vivo and in vitro, and the mechanism may be explained by HDAC6 gene inhibition.

关 键 词：组蛋白去乙酰化酶 卵巢癌 曲古抑菌素A 

分 类 号：R737.31[医药卫生—肿瘤]