三种细胞因子对恶性肿瘤多药耐受影响的实验研究

摘要

Multidrug-resistance (MDR) subline of bladder carcinoma EJ/MRP and MDR sublines of nasopharyngeal carcinoma LCE/VP and LCE/Fu were established by transfection with multidrug-resistant associ ated protein (MRP) gene and by VP-16 or5-Fu selection in vitro, respectively. The influence of cytokines rhGCSF, IFN-α1b , IL-2 on MDR cells was observed. The results showed that IFN-αlb and IL-2 could reverse drug-resistance of MDR cells to VP-16 in certain extent with the reversal times being from 3.4 to 5. 2, and increase the intracellular Daunorubicin (Dau) accumulation in MDR cells. On the contrary, rhG-CSF could enhance drug-resistance of MDR cells to VP-16 and decrease the intracellular Dau accumulation in MDR cells.The above findings revealed that IFN-α1b and IL-2 could reverse MDR of cancer cells mediated by P-gp and (or) MRP. However, rhG-CSF could enhance MDR mediated by P-gp and (or) MRP.%通过体外转染多药耐受相关蛋白(MRP)基因和化疗药物VP-16、5-Fu诱导的方法分别建立了膀胱癌多药耐受(MDR)细胞亚系EJ／MRP和鼻咽癌MDR亚系LCE／VP、LCE／Fu，并观察了细胞因子rhG-CSF、IFN-αlb和IL2对这些亚系MDR水平的影响。结果发现IFNalb和IL-2可以一定程度地逆转3种MDR细胞对VP-16耐受程度，逆转倍数在3．4与5．2之间，可以增加柔红霉素Dau在MDR细胞内的聚集程度；相反地，rhG-CSF增强了MDR细胞对VP-16的耐受程度和降低了Dau的胞内聚集程度。以上揭示IFNalb、IL-2对P-gp或(和)MRP介导的MDR具有逆转作用，rhG-CSF则增强了P-gp或(和)MRP介导的MDR程度，这为MDR研究和临床癌症治疗提供了一定参考。