三种细胞因子对恶性肿瘤多药耐受影响的实验研究

Experimental Studies on the Influence of Three Kinds of Cytokines on Multidrug Resistance of Malignant Tumors

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 L CE/ VP、L CE/ Fu,并观察了细胞因子 rh G- CSF、IFN- α1b和 IL-2对这些亚系 MDR水平的影响。结果发现 IFNα1b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 ,rh G- 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 IFNα1b、IL- 2对 P- gp或 (和 ) MRP介导的 MDR具有逆转作用 ,rh G- CSF则增强了 P- gp或 (和 ) MRP介导的 MDR程度 ,这为

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 associated protein (MRP) gene and by VP 16 or5 Fu selection in vitro , respectively. The influence of cytokines rhG CSF, IFN α1b , IL 2 on MDR cells was observed. The results showed that IFN α1b 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.