单己糖神经酰胺与卵巢癌顺铂耐药性关系的研究  

Study of ceramide monohexoside in ovarian cell line COC1/DDP resistant to cisplantin

作　　者：秦棠妮[1] 王丽莉[2] 陈洪贵[1] 高清花[1] 周荣向[1] 孙宝峥[1] 王强武[1] 

机构地区：[1]解放军第四二一医院妇产科,广州510380 [2]第一军医大学第二附属医院妇产科

出　　处：《中华妇产科杂志》2003年第9期556-559,I003,共5页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的　研究单己糖神经酰胺 (ceramidemonohexoside ,CMH)与卵巢癌顺铂耐药细胞株COC1 DDP细胞的顺铂耐药性的关系 ,及其在COC1 DDP细胞凋亡中的作用。方法　分别提取、纯化COC1 DDP细胞 (用浓度为 1 2 5、5μmol L的米非司酮处理前、后 )和卵巢癌顺铂敏感细胞株COC1细胞的中性鞘糖脂 ,用高效薄层层析、凝胶光密度成像系统分析细胞中CMH的相对含量。将COC1 DDP细胞分为 :顺铂 ( 0 1、0 2 5、0 5、1 2 5、2 5μg ml)组、米非司酮 ( 1 2 5、2 5、5、10、2 0 μmol L)组、顺铂 ( 0 1～2 5μg ml) +米非司酮 ( 1 2 5、5μmol L)组 ,用四甲基偶氮唑蓝 (MTT)法检测各组细胞的生存率、琼脂糖凝胶电泳检测各组细胞DNA的变化、透射电子显微镜观察各组细胞的形态变化。结果　COC1 DDP细胞中CMH的相对含量为 ( 3 7 1± 3 3 ) % ,明显高于COC1细胞的 ( 14 1± 1 4) % (P <0 0 0 1) ;COC1 DDP细胞分别经 1 2 5、5μmol L米非司酮处理后 ,CMH的相对含量下降到 ( 2 6 6± 2 6) %和 ( 17 5±0 7) % ,分别与米非司酮处理前比较 ,差异均有显著性 (P <0 0 5,0 0 0 1)。MTT法检测显示 ,米非司酮浓度在 5μmol L以下时 ,对COC1 DDP细胞不产生明显的抑制作用 (P >0 0 5) ;顺铂 +米非司酮组COC1 DDP细胞抑制率较?Objective To investigate the effect of ceramide monohexoside(CMH)on resistance to cisplatin and apoptosis in ovarian cell line COC1/DDP, and to provide new ideals and clues to seek new effective methods for studying the mechanism and reversing the resistance in ovarian cell line as well Methods COC1 cells and COC1/DDP cells (before and after the treatment of mifepristone) were collected and neutral glycosphingolipids (N GSLs) of the cells was isolated and purified, changes of CMH content were analyzed by high performance thin layer chromatography (HPTLC) The COC1/DDP cells were devided into three groups, one treated by cisplatin, one treated by mifepristone, the other treated by cisplatin and mifepristone The survival rate of cells in three groups were evaluated by the methyl thiazolyl tetrazolium (MTT) assay, DNA ladders were presented by DNA gel electrophoresis, the forms of cells were observed by transmission electron microscope (TEM) Results The levels of CMH were(37 1±3 3)% in COC1/DDP,higher than that in COC1(14 1±1 4)% ( P <0 001) After treating by 1 25, 5 μmol/L mifepristone, the CMH were (26 6±2 6)%( P <0 05)and(17 5±0 7)%( P <0 001), respectively Mifepristone had no effect on the viability of COC1/DDP cell below a consentration of 5 μmol/L But when mifepristone of 1 25 or 5 μmol/L combined with cisplatin at a concentration of 0 1,0 25,0 5,1 25,2 5 μg/ml,the inhibition rate of COC1/DDP cell is higher than that of COC1/DDP cells only treamed by cisplatin at the concentration of 0 1 to 2 5 μg/ml( P <0 001) The combined treatment elicited DNA fragmentation, however, neither cisplatin of 1 25 μg/ml nor mifepristone of 5 μmol/L alone could potentiate DNA fragmentation After the combined treatment, the COC1/DDP cells produced apoptosis body Conclusions CMH is related with resistance to cisplantin in ovarian cell line COC1/DDP When CMH of COC1/DDP cells was inhibited by mifepristone , the cells were sensitive to cisplatin and apoptosis was

关 键 词：单己糖神经酰胺 卵巢癌 顺铂 耐药性 治疗 

分 类 号：R737.31[医药卫生—肿瘤]