环氧化酶1与肿瘤发生之间的关系研究  

Relationships between cyclooxygenase-1 and tumorigenesis

作　　者：石茂华[1] 余鹰[2] 周洁[1] 

机构地区：[1]中山大学中山医学院人类病毒研究所,广州510080 [2]中国科学院上海生命科学研究院营养科学所

出　　处：《海军医学杂志》2013年第3期145-150,共6页Journal of Navy Medicine

基　　金：国家自然科学基金资助项目(81030004;81072397);国家重点基础研究发展计划项目(2012CB524900);教育部高等学校博士学科点专项科研基金项目(20100171110048)

摘　　要：目的研究环氧化酶1(COX-1)与肿瘤发生发展之间的关系,并探讨其机制。方法使用野生型(WT)和环氧化酶1基因敲除(COX-1 KO)小鼠,建立肿瘤小鼠模型,观察肿瘤体积变化和小鼠生存时间,绘制肿瘤体积变化曲线和小鼠生存曲线;采用流式细胞计数,检测小鼠脾脏中髓源性抑制细胞(MDSC)和体外诱导分化骨髓细胞中树突状细胞(DC)和MDSC的比例;采用荧光定量PCR检测MDSC增殖相关因子的mRNA表达水平。结果 COX-1 KO荷瘤小鼠,肿瘤生长速度加快,生存时间缩短;COX-1与骨髓细胞的分化成熟密切相关,COX-1基因敲除以后,骨髓细胞分化成熟障碍,成熟的免疫细胞减少而MDSC大量产生;荧光定量PCR结果显示,COX-1基因敲除以后钙结合蛋白S100A8、S100A9,细胞因子IL-10、VEGF表达水平显著升高,可能参与介导了COX-1抑制引起的MDSC聚集。结论 COX-1抑制可促进MDSC的产生和聚集,导致机体免疫功能的抑制,从而促进肿瘤的发展进程。Objective To investigate the relationships between cyclooxygenase-1 （COX-1） and tumorigenesis and the un- derlying mechanism. Methods Tumor models were established by using wild-type （WT） and COX-1 KO mice. Then, changes in tumor volumes and survival time were closely observed, and curves of volume change in tumor and survival time were plotted on the chart. The proportion of myeloid-derived suppressor cells （MDSC） and DC in the spleens of tumor bearing mice and bone marrow cells was analyzed with flow cytometry. The expression level of mRNA in the MDSC proliferative factor was measured by quantitative real-time PCR. Results COX-1 was implicated in the development of tumorigenesis. Tumor growth was accelerated and survival time was shortened in COX-1 KO mice. COX-1 was closely correlated with the differentiation and maturity of bone marrow cells. Disorder of bone marrow cell differentiation and maturity occurred, following gene knock-out of COX-1, and in the meantime, mature immune cells decreased and the generation and accumulation of MDSC occurred. Results of fluorimetric quantitative PCR indicated that levels of S100A8, S100A9, IL-10 and VEGF increased prominently, implying that cesium-binding protein might be involved in the accumulation of MDSC induced by COX-1 suppression, following gene knock-out of COX-1. Conclusion COX-1 might promote the generation and accumulation of MDSC, resulting in the suppression of the immune system and further promoting tumorigenesis in the tumor-bearing mice.

关 键 词：环氧化酶1 髓源性抑制细胞 肿瘤免疫逃逸 

分 类 号：R73-3[医药卫生—肿瘤]