葡萄糖神经酰胺合成酶与肿瘤多药耐药

Effects of Glucosylceramide Synthase and Multidrug Resistance of Tumors

多药耐药(multidrug resistence,MDR)是肿瘤化疗失败的主要原因,多年来医学界一直致力于多药耐药机制的研究。神经酰胺信号系统在细胞凋亡中的作用逐渐引起人们的重视,神经酰胺是细胞凋亡过程中的第二信使,葡萄糖神经酰胺合成酶(glucosylceramide synthase,GCS)可以催化神经酰胺糖基化,使其转变为无细胞毒性的葡萄糖神经酰胺,进而促进鞘糖脂的合成,大量研究表明细胞内GCS水平的增高与MDR表型有关。

Multidrug resistance is considered to be the main obstacle to the effective chemotherapeutic treatment, and has been investigated for years. The sphingolipid ceramide has now become a subject of considerable interest as an intracellular signaling molecule involved in the mediation of apoptosis. In addition to its role as a mediator of cell death, recent studies demonstrated that glucosylceramide synthase （GCS） can catalyze the glycosylation of ceramide, thereby converting it to noncytotoxic glucosylceramide （GlcCer） and promoting the synthesis of sphingolipid. Elevated levels of GlcCer have been found to be related to the phenotypes of a number of multidrug-resistant human cancer cell lines.