Chemopreventive Effect of Hamster Pancreatic Cancer

Katsumichi Iki, Toshimitsu Majima, Tadahiko Kubozoe, Sueharu Iwamoto, Eisi Onuma and Tsukasa Tsunoda

Department of Surgery, Division of Gastroenterology, Kawasaki Medical School

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-3206 inhibited 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 7 weeks, the numbers of pancreatic nodules were significantly reduced in administered group from 46 days after BOP initiation onward. Zymographic analysis showed that the gelatinolytic activity of proMMP-2 and activeMMP-2 was detected in control group. On the 0.1 and 0.2% OPB-3206 diet proMMP-2 activity was increased, but that of activeMMP-2 became undetectable. The results thus suggest that OPB-3206 selectively inhibits carcinogenesis in hamster pancreas by inhibiting MMP-2 activation.

Key words
matrix metalloproteinase, chemoprevention, pancreatic cancer

Reprint requests
Katsumichi Iki Department of Surgery, Division of Gastroenterology, Kawasaki Medical School 577 Matsushima, Kurashiki, 701-0192 JAPAN

Accepted
December 22, 1999

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