【摘要】 目的:探讨葡萄糖神经酰胺合成酶(glucosylceramide synthase,GCS)基因的表达与急性白血病患者耐药的相关性。方法:以β-actin基因为内参照物,采用RT-PCR方法分析了36例耐药/非耐药急性白血病患者血标本中GCS基因及经典的多药耐药基因(mdr1)的表达情况;并同时对标本中的BCL-2基因和BAX基因的表达水平亦进行了检测,以初步探讨GCS基因导致肿瘤细胞耐药的机制。结果:急性白血病耐药组标本的GCS基因及mdr1基因的扩增条带吸光度(A)相对比值均明显高于非耐药组(P<0.001)。耐药组BCL-2基因扩增条带A相对比值同样明显高于非耐药组(P<0.001),而BAX基因的表达则明显低于非耐药组(P<0.01),BCL/BAX比值在耐药及非耐药组之间差异有显著性(P<0.01)。结论:GCS基因在急性白血病细胞耐药的形成过程中可能起重要作用,且GCS促进肿瘤细胞耐药的机制可能与其通过催化神经酰胺糖基化从而影响凋亡相关基因的表达有关。更多还原

【Abstract】 Objective:To explore the relationship between the expression of glucosylceramide synthase(GCS) gene and multidrug resistance MDR in human leukemia. Methods:Using β-actin gene as internal reference, the level of GCS, mdr1, BCL-2 and BAX gene in 36 clinical multidrug resistance/non-resistance blood samples with acute leukemia were detected by RT-PCR technique. Results:The relative quantities of GCS and mdr1 genes in multidrug resistance group were significantly increased compared with non-resistance group(P < 0.001). The expression of BCL-2 gene in multidrug resistance samples was also significantly higher than that in non-resistance group(P < 0.001), but the expression of BAX gene was significantly lower in multidrug resistance group(P < 0.01). There was a significant difference in BCL-2/BAX ratio between multidrug resistance and non-resistance groups. Conclusion:The high expression of GCS gene is possibly correlated with multidrug resistance in acute leukymia, and cell apoptosis might be one of the main molecular pathology mechanisms of multidrug resistance caused by GCS gene.更多还原