摘要
目的 探讨选择性环氧化酶-2(cyclooxygenase-2,COX-2)抑制剂塞来昔布(celecoxib)对大鼠脑胶质瘤免疫微环境及生物学行为的影响.方法 建立大鼠脑胶质瘤模型,观察celecoxib治疗后肿瘤大小及大鼠生存期;免疫组化法检测肿瘤组织COX-2、转化生长因子-β(transforming growth factor-beta,TGF-β)、血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白表达;流式细胞术检测肿瘤微环境CD4+CD25+T细胞亚群数量;酶联免疫法(ELISA)检测大鼠血清中前列环素E2(Prostaglandin E2,PGE2)、白介素-l0(IL-l0)、白介素-12(IL-12)分泌水平.结果 Celecoxib治疗组肿瘤体积明显小于对照组[(103.67±5.54) mm3,(151.60±8.34) mm3,P<0.01],并可延长大鼠生存期[(42.87± 1.72)d,(26.13± 1.53)d,P<0.01],肿瘤组织中COX-2、VEGF及TGF-β蛋白的表达均出现下调,其肿瘤微环境中CD4+CD25+T细胞亚群比例明显降低(5.32%,7.84%,P<0.05).血清中PGE2与IL-10水平明显下降[(223.66±33.79)pg/ml,(344.15±41.09) pg/ml,(98.69± 10.99) pg/ml,(133.37± 13.15) pg/ml,P<0.01],而IL-12分泌明显增多[(237.20±37.31) pg/ml,(117.90±19.20) pg/ml,P<0.01].结论 Celecoxib可通过多种途径改善肿瘤局部免疫微环境,从而改变肿瘤的生物学行为,延缓肿瘤发展,并为肿瘤治疗提供良好的基础环境.
Objective To investigate the effect of celecoxib,a selective inhibitor of cyclooxygenase-2 (COX-2),on glioma immune microenvironment and biological action in rat.Methods After treated with celecoxib,tumor volume and survive time were observed in a rat glioma model.COX-2,transforming growth factor-beta (TGF-β) and vascular endothelial growth factor(VEGF) expression in tumor tissue were detected using immunehistory and CD4 + CD25 + T cells was detected by flowcytometry.By using enzyme-linked immunosorbent assay (ELISA),the production of prostaglandin(PGE2),interlukin 10(IL-10) and interlukin 12(IL-12) were detected in rat serum.Results Tumor volume decreased after treated with celecoxib ((103.67±5.54) mm3,(151.60±8.34)mm3,P<0.01) and survive time of animals were prolonged ((42.87±1.72) d,(26.13±1.53)d,P<0.01).Expression of COX-2,TGF-β and VEGF in tumor tissue was down regulated after treated with celecoxib and number of CD4+CD25 + T cells were decreased (5.32%,7.84%,P< 0.05).PGE2,IL-10 production in serum was obviously decreased by treatment of celecoxib ((223.66±33.79) pg/ml,(344.15±41.09) pg/ml,(98.69± 10.99) pg/ml,(133.37± 13.15) pg/ml,P<0.01) while the production of IL-12 was increased ((237.20±37.31) pg/ml,(117.90±19.20) pg/ml,P<0.01).Conclusion Celecoxib may improve the status of immunosuppression of rat glioma by several pass ways and modify tumor biological action.Celecoxib may give a good microenvironment for immunotherapy of gliomas.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2014年第2期107-109,共3页
Chinese Journal of Behavioral Medicine and Brain Science
基金
山东省自然科学基金项目(ZR2009CQ015)