Dynamic Alteration Of Gelatinase In Liver Tissue And Effection Of Matrix Metalloproteinase Inhibitor BB-94 On Tumor Growth During Experimental Hepatocarcinogenesis

Background: Matrix metalloproteinases(MMPs) are zinc proteinases that degrade compounds of the extracellular matrix (ECM). Many studies have demonstrated that degradation of extracellular matrix (ECM),particularly basement membrances, is required for tumor progression, invasion and metastasis. The gelatinases or type IV collagenases (72-kDa MMP-2 and 92-kDa MMP-9) are the enzymes that degrade the basement member and have been most studied. Hepatocellular carcinoma (HCC) is a common malignancy in our country, but the molecular mechanisms of HCC in growth , invasion and metastasis is not clarified. To address the contribution of MMP activity to the development of hepatocellular carcinoma, we administered the synthetic MMP inhibitor batimastat(BB-94) in experimental rat hepatomas model induced by DENA, and determined MMP-2 and MMP-9 activity in liver tissues from rat treated with and without batimastat(BB-94). Objective: To investigate the dynamic alteration of the latent and activated forms of MMP-2 and MMP-9 in rat liver tissue during experimental hepatocarcinogenesis and the effects of matrix metalloproteinase inhibitor BB-94 on the growth and invasion and metastasis of hepatocellular carcinoma. Methods and Results: 1. Hepatocellular carcinomas were induced with the administration of diethy lnitrosoamine (DENA) in Waster rats . At the stages of procancerous lesions(8, I2week) and hepatocellular carcinoma (16, ZOweek), BB-94 was intraperitoneally injected to treat the experimental hepatomas model of Wistar rats . The area of tumor nodules of batimastat-treated group(20 wk) was significantly smaller than those of controls.( 5.8?.6mm2 vs 13.2?12.4 mm2, t=2.532, p