Objective To study the effect of immunotherapy by using cyclooxygenase-2(COX-2)inhibitors combined with interleukin-2(IL-2)and its mechanism in mice Renca cell kidney cancer.Methods After a mouse model of ectopic kidney cancer was established,all 28 mice were divided into 4 groups randomly and treated with different methods(IL-2,NS-398,IL-2 + NS-398 and PBS,respectively).Then peripheral blood in tumor-bearing mice was extracted on the 14th day and the 28th day,which were analyzed by flow cytometry to know the changes of regulatory T cells(Treg).The tumors and spleens were all taken off in the end,and immunohistochemistry was used to detect Treg expression.Results COX-2 inhibitors combined with IL-2 treatment can suppress the tumor growth of Renca cell kidney cancer significantly(P＜ 0.05).COX-2 inhibitors can also down-regulate the expression of Treg in tumor-bearing mice peripheral blood,intra-tumor and spleen.This combination shows synergistic effects.Conclusions COX-2 inhibitors combined with IL-2 can significantly suppress the development of ectopic kidney cancer in mice,which indicate that Treg reduction may be one of the mechanisms of kidney cancer growth inhibition.%目的 探讨环氧化酶-2(cyclooxygenase-2,COX-2)抑制剂联合白细胞介素-2(interleukin-2,IL-2)对小鼠肾癌免疫治疗的作用及其机制.方法 以Renca细胞建立Babl/c小鼠异位肾癌模型,共28只,随机等分成4组,不同组别予以不同给药,分别为IL-2组、NS-398(一种COX-2抑制剂)组、IL-2+ NS-398组和空白对照组.在第14天、28天提取各组荷瘤小鼠外周血,用流式细胞术检测调节性T细胞(regulatory T cells,Treg)的变化；切取荷瘤小鼠瘤体及脾脏,免疫组化检测小鼠脾脏和肿瘤局部Treg的变化.结果 小鼠异位肾癌在不同药物处理后,肿瘤体积出现明显变化,联合用药组肿瘤体积减小明显,经多组t检验,与其他组相比差异有统计学意义(P＜0.05).同时,COX-2抑制剂能下调荷瘤小鼠外周血、肿瘤及脾脏中Treg的表达,且与IL-2联合有协同作用(P＜0.05).结论 COX-2抑制剂联合IL-2可显著抑制荷瘤小鼠异位肾癌的发展,说明Treg的下调是抑制肾癌生长的可能机制之一.
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