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 Hakamoris 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.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2001年第8期827-830,共4页
Chinese Journal of Cancer
