Inhibition of Pancreatic Carcinogenesis by Shark Cartilage Proteoglycan in Hamsters

Abstract

Effects of shark cartilage proteoglycan (SCPG), which has heat-stable inhibitory activities against matrix metalloproteinase (MMP)-2 and -9 in vitro, on pancreatic carcinogenesis were studied in a rapid production model for pancreatic duct adenocarcinomas (PCs) in hamsters. Female Syrian golden hamsters received a diet containing 0% (group 1), 0.2% (group 2) or 0.4% (group 3) of SCPG for 50 days after initiation with N-nitrosobis(2-oxopropyl)amine followed by augmentation pressure. The number of PCs were 3.1 ± 2.0 in group 1 and 1.4 ± 0.9 in group 3, and total ductal lesions including hyperplasia, atypical hyperplasia and PCs were 9.7 ± 4.0 and 5.6 ± 2.7, respectively, the differences being significantly different (P < 0.05). These results were confirmed in a repeat experiment (P < 0.01). Gelatin zymography revealed that oral administration of SCPG did not affect the expression and activation of MMP-2 and MMP-9 in either serum or PC tissue. These results suggest that inhibition of pancreatic carcinogenesis by SCPG might involve a mechanism different from other synthetic-MMPs inhibitors.