葡萄糖神经酰胺合成酶在肿瘤多药耐药中的研究

葡萄糖神经酰胺合成酶(GCS)参与神经酰胺(Cer)糖基化代谢途径,能阻断Cer对细胞凋亡信号的转导.研究表明在多种肿瘤多药耐药细胞株中GCS含量增加且与耐药表型相关,GCS和P-糖蛋白(P-gP)在细胞耐药的生物学机制中有相关性.通过化学抑制剂以及RNA干扰技术下调GCS的水平和活性能增强肿瘤细胞对药物的敏感性.因此,抑制GCS是逆转肿瘤多药耐药的一种新机制.

Glucosylceramide synthase in tumor multidrug- resistance

Glucosylceramide synthase(GCS) plays an important role in ceramide metabolism and can block apoptosis signal pathway which is mediated by ceramide. Recently, studies have demonstrated that overex-pression of GCS exists in various muhidrug resistant cancer cell lines and is related to drug resistant pheno-type. A possible connection between GCS and P-gp is also suggested. Moreover,the level of GCS can be down-regulated to increase tumor cells sensitivity by chemical inhibitor and RNA interference. Thus, inhibition of ac-tivity and expression of GCS is a new mechanism of reversing muhidrug resistance.