PPMP对人白血病多药耐药细胞凋亡相关基因的影响

摘要

目的 研究苯基棕榈酰胺吗啡丙醇( PPMP)对人红白血病多药耐药细胞K562/AO2葡萄糖神经酰胺合成酶(GCS)基因的调节及对凋亡相关基因的影响.方法 应用体外细胞培养技术观察GCS特异性化学抑制剂PPMP对K562/AO2细胞GCS基因的抑制作用,采用RT-PCR技术分析GCS基因被抑制前后K562/AO2细胞中GCS、B细胞淋巴瘤-白血病2(Bcl-2)和Bcl相关X蛋白(Bax)基因的表达.结果 PPMP可抑制K562/AO2细胞GCS mRNA的表达,同时致相应细胞的Bcl-2基因表达下降;但Bax基因则无明显变化.结论 GCS可能是通过Bcl-2信号转导途径使细胞的抗凋亡能力增强,从而导致白血病细胞的多药耐药.%Objective To explore the effect of l-phenyI-2-palmitoylamino-3-morpholino-l-propanal(PPMP) on glucosylceramide synthase gene (GCS)-induced multidrug resistance human leukemia cell strain K562/AO2 and apoptosis-related genes. Methods The K562/AO2 cells were treated with PPMP, the mRNA expressions of GCS, Bcl-2 and Bax were analyzed with RT-PCR. Results PPMP could inhibit GCS mRNA expression in K562/AO2 cell strain with downregulating Bcl-2 mRNA expression, but without apparent change of Bax mRNA expressioa Conclusion GCS gene may lead to multidrug resistance of human erythroleukemia cell strain K562/AO2 by enhancing anti-apoptosis of the cells via Bcl-2 signal transduction.