Experimental Study On The Reversal Of Multidrug Resistance Of Human Lung Adenocarcinoma Cell Line By Interleukin2 And Interleukin12

Objective To investigate the reversal effect of human recombinant interleukin2(IL2)and interleukin 12 (IL12) onmultidrugresistance (MDR) of human lung adenocarcinoma cell line A549/ADM and its possible mechanism. Methods We induced human lung adenocarcinoma cell line A549 into multidrug resistant cell line A549/ADM through step-wise selection with adriamycin,establishing a MDR cell model;evaluated the effects of the human IL2, IL12 and their combination on the mdrl gene expression at the protein level with monoclonal antibody by immuno flow cytometry. P-glycoprotein function was examined after accumulation of the fluorescent drug,adriamycin by flow cytometry. Chemosensitivity to adriamycin was analyzed using the MTT assay. Results Overexpresion of P-gp (the positive rate of P-gp expression was92±1.5% ) was found in A549/ADM cells,while the P-gp couid only be detected in (2.5±0.5) % of A549cells,the difference was significant (P<0.01) . IL2, IL12 and their combination couid downregulate P-gp expression ,enhance the intracellular accumulation of adriamycin ,and improve the chemosensitivity of adriamycin .moreover the combination of IL2 and IL12 had additive effect. This cytokine-induced reversal of MDR was strongly time dependent,with maximal effects after 48 and 72h of cytokine treatment. Conclusion The treatment of tumor cells with a longterm, intermitted singular and unefficient chemotherapeutic agent is capable of causing acquired MDR. 1L2 and IL12 can reverse the MDR by inhibiting P-gp expression and increasingthe accumulation of intracellular chemotherapeutic agents in tumor cells. The potential of cytokines for MDR reversal,makes cytokine pretreatment an attractive approach for improving the response of chemotherapy.The present results suggest additional possibilities for more sophisticated combination therapies involving cytokines and MDR -related drugs.