Expression Of Matrix Metalloproteinase-9 In Gastric Cancer And Marimastat Inhibits Growth And Metastasis Of Human Gastric Cancer In Nude Mice

Objective1. To study the effect of MMP-9 on growth, metastasis in gastric cancer by evaluating the relationship between the expression of MMP-9 and microvessel density(MVD), the size of tumor and metastasis in gastric cancer tissues, paracancerous tissues, and incisal margin normal tissues.2. The aim of study is to determine the effects of matrix metalloproteinase inhibitor Marimastat on the growth and metastasis of human gastric cancer in nude mice. Methods1. A total of 63 specimens resected were investigated by En Vision immunohistochemical staining with a anti-MMP-9 monoclonal antibody and a monoclonal antibodies against FVIII Rag. The expression of MMP-9 and MVD in various region of the gastric cancer tissues, paracancerous tissues and incisal margin normal tissues were detected and the relationship between the expression of MMP-9 and MVD, as well as their relationship with lymph node, and liver metastasis were analyzed.2. Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. These nude mice have been randomly divided into 4 groups. Control group receiving saline solution, group receiving 5-FU, group receiving Marimastat and group receiving 5-FU combined with Marimastat. 5-FU and Marimastat were given i.p.every other day for eight weeks. Nine weeks after implantation, the mice were sacrificed and the tumor volum, inhibition rates, microvessel density, the presence of metastasis were evaluated respectively.Results1. The rate of high expression of MMP-9 in cancer tissues was significantly higher than in the paracancerous tissues (P<0.01). The rate of low expression of MMP-9 in the paracancerous tissues was significantly higher than in the normal tissues(P<0.01). theexpression of MMP-9 was correlated with angiogenesis. The MVD in the high expression of MMP-9 was significantly higher than in those with the low expression of MMP-9 in cancer tissues and paracancerous tissues (p<0.05) . Moreover, the high expression of MMP-9 and MVD in cancer tissures were related with lymph node, and liver metastasis . 2. Compared with the control group, both 5-FU and Marimastat significantly inhibited the growth of tumors; the effect of inhibition was more significant than single agent in the combinated group. The inhibition rates were 0%, 50.9%, 52.7%, 86.1% respectively. High expression of MMP-9 , the hepatic metastasis and the microvessel density were significantly inhibited in Marimastat group and combined group than that in 5-FU group. Conclusions1. MMP-9 is important for growth and metastasis in gastric cancer. MMP-9 may affect the metastasis of gastric cancer by promotion of angiogenesis.2. Marimastat has strong inhibitory effect both on growth and metastasis of human gastric cancer in nude mice. It may be more effective when combined with cyotoxic agents.