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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 investigate the effects of phenyl palmitamide morphinopropanol (PPMP) on the regulation of glucose ceramide synthase (K562 / AO2) gene in human erythroleukemia multidrug resistant cell line K562 / AO2 and its effect on apoptosis related genes. Methods GCS-specific chemical inhibitor PPMP was used to observe the inhibitory effect of GCS on GCS in K562 / AO2 cells by in vitro cell culture technique. GCS gene was analyzed by RT-PCR before and after inhibition of GCS gene in GCS, B-cell lymphoma-leukemia 2 (Bcl-2) and Bcl-related protein X (Bax) gene expression. Results PPMP inhibited the expression of GCS mRNA in K562 / AO2 cells, while the expression of Bcl-2 gene in the corresponding cells decreased. However, Bax gene did not change significantly. Conclusion GCS may enhance the anti-apoptotic ability of cells through Bcl-2 signal transduction pathway, leading to multidrug resistance of leukemic cells.