卵巢癌细胞株SKOV_3/ADM的多药耐药性逆转研究  

Study of Multidrug Resistance Reversion in Ovarian Cancer Cell Line SKOV_3/ADM

作　　者：袁匀[1] 王丽莉[1] 张积仁[2] 

机构地区：[1]第一军医大学附属珠江医院妇产科,广东广州510282 [2]第一军医大学附属珠江医院肿瘤中心,广东广州510282

出　　处：《癌症》2001年第8期827-830,共4页Chinese Journal of Cancer

摘　　要：目的:研究糖脂合成酶抑制剂苯基棕榈酰胺吗啡丙醇(DLthreo1phenyl2palmitoylamino3morpholino1propanol,PPMP)对卵巢癌多药耐药细胞株SKOV3/ADM的中性鞘糖脂成分——单己糖神经酰胺(monohexosylceramide,CMH)含量的影响,探讨PPMP对SKOV3/ADM多药耐药性的逆转作用。方法:收集SKOV3细胞和PPMP处理前后的SKOV3/ADM细胞,采用改良的Hakamoris方法提取中性鞘糖脂,用高效薄层层析技术(HPTLC)分析CMH含量变化,用体外细胞毒实验技术(MTT)检测PPMP对SKOV3/ADM耐药性的逆转作用。结果:耐药株SKOV3/ADM与其敏感株SKOV3相比,CMH含量明显增高,25μmol/LPPMP作用SKOV3/ADM细胞48h,可完全抑制其CMH的合成;PPMP可增加SKOV3/ADM细胞对阿霉素、长春新碱的敏感性,但PPMP浓度不同时这种作用没有显著性差异。结论:糖脂合成酶抑制剂PPMP可有效抑制多药耐药卵巢癌细胞的中性鞘糖脂成分CMH的合成,并对卵巢癌细胞多药耐药性有逆转作用。Objective: To investigate the effects of PPMP (DL threo 1 phenyl 2 palmitoylamino 3 morpholino 1 propanol),a glycolipids synthase inhibitor, on the modulation of monohexosylceramide (CMH), ingredient of neutral glycosphingolipids, and multidrug resistance reversion (MDR) in ovarian cancer cell line SKOV3/ADM. Methods: Adriamycin (ADM) resistant SKOV3 (SKOV3/ADM) cells were treated with PPMP in different acceptable concentration in vitro. SKOV3 and SKOV3/ADM (before and after PPMP treatment) cells were collected and N GSLs (neutral glycosphingolipids) of the cells was isolated and purified with the modified Hakamoris method. Changes of CMH content were analyzed by HPTLC (high performance thin layer chromatography). The effects of PPMP, on the reversion of MDR in SKOV3/ADM was determined by MTT (thiazolyl blue) method. Results: The levels of CMH in SKOV3/ADM cells were significantly higher than those in SKOV3 cells. The synthesis of CMH in SKOV3/ADM can be completely inhibited by PPMP treatmeat at 25 μmol/L for 48 h, 44% inhibition by PPMP at 15 μmol/L and 40% at 5 μmol/L PPMP increased sensitivity of multidrug resistant SKOV3/ADM cells to Adriamycin and Vincristine. This effect of PPMP in different concentration was not significant differeat. Conclusion: PPMP, a chemical inhibitor of glycolipids synthase, can effectively inhibit CMH synthesis in ovarian cancer MDR cell line SKOV3/ADM, and PPMP possesses MDR reversing activity in ovarian cancer.

关 键 词：糖脂 卵巢肿瘤 多药耐药性 细胞株 逆转作用 SKOV3/ADM 

分 类 号：R737.31[医药卫生—肿瘤]