基础医学与临床 ›› 2013, Vol. 33 ›› Issue (9): 1129-1134.

• 研究论文 • 上一篇    下一篇

曲古抑菌素A体内外杀伤卵巢癌细胞

张美花,金海丹,朴俊杰,林贞花,金铁峰   

  1. 延边大学基础医学院
  • 收稿日期:2012-08-28 修回日期:2013-01-04 出版日期:2013-09-05 发布日期:2013-08-28
  • 通讯作者: 金铁峰 E-mail:jintf@ybu.edu.cn
  • 基金资助:
    胞质NPM突变蛋白调控TRAF6介导的AKT泛素化激活在急性髓系白血病中的作用;吉林省科技厅社会发展重点项目;吉林省教育厅“十二五”科学技术研究项目

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

  • Received:2012-08-28 Revised:2013-01-04 Online:2013-09-05 Published:2013-08-28
  • Contact: Tie-Feng Jin E-mail:jintf@ybu.edu.cn

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。

关键词: 组蛋白去乙酰化酶, 卵巢癌, 曲古抑菌素A

Abstract: Objectives To investigate the killing effect and mechanism of histone deacetylase inhibitor, trichostatin A (TSA), on ovarian cancer. Methods The killing effect of TSA on ovarian cancers was detected by using XTT 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 compared with normal ovarian epithelial cell lines (P<0.05). Also, the ratio of apoptosis and cell death were significantly higher in TSA treated ovarian cancer cells than it in the untreated group. In vivo experiments also showed that ES-2 xenograft treated by TSA was growing much slower compared with untreated ES-2 xenograft. Conclusions TSA could effectively kill the ovarian cancer cells in vivo and in vitro, and the mechanism might be carried out partially by HDAC6 gene inhibition.

Key words: Histone Deacetylase, Ovarian Cancer, Trichostatin A