巨噬细胞金属弹性蛋白酶抑制小鼠结肠癌中bFGF表达的实验研究  

Experimental Study on Suppression of bFGF Expression by Macrophage Metalloelastase in Murine Colon Cancer

作　　者：徐张巍[1] 许建明[1] 石海[1] 梅俏[1] 

机构地区：[1]安徽医科大学第一附属医院消化内科,230031

出　　处：《胃肠病学》2011年第4期206-210,共5页Chinese Journal of Gastroenterology

基　　金：安徽省自然科学基金项目资助(01043904)

摘　　要：背景:巨噬细胞金属弹性蛋白酶(MME)为基质金属蛋白酶(MMPs)家族成员之一,目前研究认为其具有产生血管抑素、抑制肿瘤血管生成的作用。目的:探讨MME对小鼠结肠癌中的血管生成因子碱性成纤维细胞生长因子(bFGF)表达的影响。方法:应用稳定转染MME的小鼠结肠癌细胞株CT-26建立小鼠皮下移植瘤模型,观察皮下肿瘤生长情况。以实时荧光定量RT-PCR、免疫组化染色和蛋白质印迹法检测肿瘤组织中的MME、bFGF表达。结果:接种CT-26细胞4周后,MME转染组小鼠皮下肿瘤组织中可检测到MME蛋白表达。该组4周内死亡率和皮下肿瘤平均体积显著低于空质粒转染组和未转染组(P<0.05),肿瘤组织中的bFGF mRNA和蛋白表达量以及蛋白表达阳性率亦显著低于两对照组(P<0.05)。两对照组间上述指标均无明显差异。结论:MME对小鼠结肠癌中的bFGF表达以及肿瘤生长具有抑制作用。Macrophage metalloelastase （MME） is a member of matrix metalloproteinases （MMPs） family, which can generate angiostatin and is a potent inhibitor of tumor angiogenesis. Aims： To investigate the effect of MME on expression of basic fibroblast growth factor （bFGF）, an angiogenesis factor, in murine colon cancer. Methods： Murine colon cancer cell line CT-26 stably transfected with MME was inoculated subcutaneously into mouse to establish the transplanted tumor model, and the tumor growth was observed continuously. Real time fluorescent quantitative RT-PCR, immunohistochemistry and Western blotting were used to deterrnine the expressions of MME and bFGF in tumor tissues. Results： Four weeks after inoculation of CT-26 cells, expression of MME protein could be detected in subcutaneous tumor tissues of mice in MME-transfected group. The 4-week mortality rate and mean tumor volume were significantly lower in MME-transfected group than those in vector-transfected group and non-transfected group （P〈0.05）. The expression levels of bFGF mRNA and protein, as well as the immunoreactive positivity rate in tumor tissues, were significantly lower in MME-transfected group （P〈0.05） and no significant difference was observed between the two control groups. Conclusions： MME can inhibit bFGF expression and retard tumor growth in murine colon cancer.

关 键 词：基质金属蛋白酶12 成纤维细胞生长因子2 肿瘤血管生成 结直肠肿瘤 模型 动物 

分 类 号：R735.35[医药卫生—肿瘤]