Abstract
In the present experiment, the effects of OPB-3206, 3S-[4-(N-hydroxyamino)-2R-isobutylsuccinyl] amino-1-methoxy-3, 4-dihydrocarbostyril, a novel metalloproteinase inhibitor, were studied on the growth of hamster pancreatic ductal carcinomas induced by a rapid production model. OPB-3206inhibited the activities of interstitial collagenase, gelatinase A and B, and stromelysis in vitro. When 0%, 0.1% and 0.2% OPB-3206 was orally administered in the diet for 7weeks, the numbers of pancreatic nodules were significantly reduced in administered group from 46days after BOP initiation onward. Zymographic analysis showed that the gelatinolytic activity of proMMP-2and activeMMP-2was detected in control group. On the 0.1and 0.2% OPB-3206diet proMMP-2activity was increased, but that of activeMMP-2became undetectable. The results thus suggest that OPB-3206selectively inhibits carcinogenesis in hamster pancreas by inhibiting MMP-2 activation.
