人巨噬细胞金属弹性蛋白酶对人胃癌细胞COX-2和VEGF体内表达的影响

目的：探讨体内人巨噬细胞金属弹性蛋白酶（HME）对人胃癌细胞环氧合酶-2和血管内皮生长因子（VEGF）表达的影响。方法：选取BALB/c nu/nu裸鼠24只构建人胃癌细胞SCG-7901裸鼠皮下移植模型，随机分为对照组和HME干预组，其中HME干预剂量分别为0.2mg/kg、0.4mg/kg、0.8mg/kg，对照组给予等体积0.9%氯化钠。干预6周后处死动物，测量鼠重、瘤重、肿瘤大小，计算抑瘤率；采用Western blot和免疫组织化学方法检测移植瘤组织中COX-2和VEGF的表达；CD34标记血管内皮细胞计数肿瘤微血管密度（MVD）。结果：与对照组相比各剂量组HME均能明显抑制皮下移植瘤生长（ P <0.05）；且在HME各剂量组中0.8mg/kg组抑瘤作用最明显。HME能明显抑制移植瘤组织中COX-2和VEGF的表达，并明显降低肿瘤MVD值（ P <0.05）。结论：HME通过抑制肿瘤微血管形成来抑制肿瘤的生长；HME抑瘤作用具有剂量依赖性。

Effects of Human Macrophage Metalloelastase on Expression of COX-2 and VEGF in vivo

Objective：To study the effects of human macrophage metalloelastase（HME） on the expression of cyclooxygenase-2（COX-2）and vascular endothelial growth factor（VEGF）in vivo. Methods：24 nude mice receiving subcutaneous injections of human gastric cancer SCG-7901 cells were randomly divided into four groups, which were treated with HME does of 0.2mg/kg, 0.4mg/kg and 0.8mg/kg, meanwhile control group was treated by equivalent normal saline. The tumors were removed after six weeks treatment,the weights and volume of which were evaluated as well as the weight of the mice. The expression of COX-2 and VEGF was detected by immunohistochemical SP method and Western Blot assay. Microvessel density（MVD） was analyzed in CD34-stained vascular endothelial cell. Results：The growth of xenografts were significantly inhibited by each does groups of HME（ P <0.05）.The depressant effect was most powerful in HME 0.8mg/kg does group among intervention groups. HME depressed the expression ofCOX-2, VEGF and MVD obviously in xenografts（ P <0.05）. Conclusion：The antitumor effect of HME in nude mice may attribute to the anti- angiogenesis in dose dependent manner.