Objective: To examine the cytotoxicity of cisplatatin(DDP) combined with Interleukin-2(IL-2) or/and Interleukin-12(IL-12) against lung adenocarcinoma A549 cell line(A549) and DDP resistant A549 cell line (A549/DDP). To explore multidrug resistant mechanisms in A549/DDP cell line. Methods: Cytotoxic testing in vitro were performed by MTT assay, The MDR1 protein,mutation of P53 protein and bcl-2 protein were detected by immunohistochemical staining. Results: The cytotoxicity of DDP alone against the two cell lines(A549 and A549/DDP) was not apparently different from that of DDP combined with IL-2, but was signficanty incereased with the IL-12 combination, and enhanced further by adding IL-2. Bcl-2, mutation of P53, MDR1 gene expression in A549/DDP cells was higher than in A549 cells. As compared with untreated A549,A549/DDP cells, the expression of mutation of P53 and bcl-2 MDR1 reduced significantly in IL-12 treated cells. Conclusion: The combined use of Il-12 and DDP had synergic cytotoxicity against A549. IL-12 could increased the sensibility of DDP against A549/DDP. This result maybe IL-12 changers the expression of mutation of P53, bcl-2 and MDR1 gene. IL-2 could enhaned above two effects further. A549/DDP cell expressed a stable multidrug resistant phenotype. The overexpression of bcl-2 gene and mutation of P53 gene in A549/DDP cell may be its one of the important mechanisms for multidrug resistance. |