白细胞介素2(IL-2)和白细胞介素12(IL-12)对肺腺癌细胞作用机制的研究

目的:探讨人肺腺癌A549/DDP的多药抗药机理。方法:采用四氮唑盐快速比色法(MTT法)进行体外细胞毒性实验;免疫组化方法检测A549及A549/DDP在细胞因子作用前后突变型P53、bc l-2、MDR1的表达。结果:IL-2与顺铂合用前顺铂对两株细胞的毒性作用无明显变化;IL-12与顺铂合用后顺铂对两株细胞的毒性作用明显增强;IL-2、IL-12与顺铂合用后顺铂对两株细胞的毒性作用进一步增强。免疫组化结果显示:IL-2作用于两株细胞后,突变型P53、bc l-2、MDR1的表达无明显变化;IL-12作用于两株细胞后,bc l-2、突变型P53、MDR1的表达均下调,IL-2能增强上述作用。结论:IL-12与顺铂具有协同抑制肺腺癌A549细胞的作用,IL-12能增加A549/DDP细胞对顺铂的敏感性,IL-2能进一步增强上述作用。

Study on mechanism of Interleukin-2 and Interleukin-12 against lung adenocarcinoma cell

Objective To detect the cytotoxicity of cisplatin(DDP) combined with Interleukin-2(IL-2) and /or Interleukin-12(IL-12) against lung adenocarcinoma A549 cell line(A549)and DDP resistant A549 cell line(A549/DDP),in order to explore the multidrug resistant mechanisms of A549/DDP.Method Cytotoxic testing in vitro was performed by MTT assay,and the expressions of mutant P53,bcl-2 and MDR-1 before and after action of cytokine 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 signficantly incereased with the IL-12 combination,and enhanced further by adding IL-2.The expression of mutant P53,Bcl-2 and MDR-1 in A549/DDP cells was higher than that in A549 cells.As compared with untreated A549 and A549/DDP cells,the expression of mutant P53,bcl-2 and MDR-1 reduced significantly in IL-12 treated cells.Conclusion The combination of IL-12 and DDP has synergic inhibition on A549 cells and IL-12 can increase the sensibility of A549/DDP on DDP maybe through changing the expression of mutant P53,bcl-2 and MDR-1,while IL-2 can enhance the above effects further.The overexpression of bcl-2 and mutant P53 in A549/DDP cells may be one of the important mechanisms for multidrug resistance.