【摘要】 目的　观察经全反式维甲酸 (RA)诱导分化的髓母细胞瘤细胞系Med 3对顺铂 (DDP)的化疗敏感性 ,死亡性质及其内在的分子机制。方法　分析RA、DDP和两者配伍对Med 3细胞形态和增殖的影响 ,观察被处理细胞的死亡特点并检测各处理因素对凋亡相关基因Fas和Fas配体 (FasL)表达水平和表达方式的影响。结果　可溶型和膜型FasL在正常培养和被处理的Med 3细胞中均呈阳性 ,Med 3细胞产生可溶型Fas并呈胞浆阳染。与DDP不同 ,RA可明显上调Fas表达并使Fas蛋白从胞浆移至细胞表面 ;但仅在它与DDP联用时 ,才能诱导靶细胞凋亡。结论　分化诱导剂RA通过修饰Fas基因表达形式 ,提高髓母细胞瘤Med 3细胞对DDP的凋亡敏感性。RA/DDP配伍方案可能成为临床治疗髓母细胞瘤的新途径。更多还原

【Abstract】 Objective To elucidate the chemosensitivity of retinoic acid (RA) differentiated medulloblastoma Med 3 cells to conventional anti cancer drug and to determine the potential genetic factor(s) mediating this sensitivity. Methods Ten μmol/L RA, 5 μg/ml cisplatin (DDP) and their combination with one half concentration of each were used respectively to treat human medulloblastoma cell line Med 3 in vitro. Cell proliferation, morphology and death pattern as well as Fas/FasL expressions were analyzed by multiple approaches. Results Both soluble and membrane FasL could be detected in the treated and untreated Med 3. Fas was positive in the cytoplasm of Med 3 cells and the cells could produce soluble Fas. DDP had no obvious effect on Fas expression. RA up regulated Fas expression and translocalization from cytoplasm to cell membrane of the treated cells. Neither RA nor DDP could trigger apoptosis but in combination could effectively induce apoptosis. Conclusion RA could enhance the apoptotic susceptibility of Med 3 cells to DDP presumably through modulating the Fas expression pattern. Combined RA/DDP regimen would have potential clinical value in the management of medulloblastomas.更多还原