Chemoprevention of Pancreatic Carcinogenesis
The present study was designed to establish if Etodolac, a selective cyclooxygenase-2 inhibitor, prevents chemically induced intraductal papillary carcinoma (IPC) in the main pancreatic duct of hamsters. Hamsters were subjected to cholecystoduodenostomy with dissection of the distal end of the common duct. Four weeks after surgery, the surviving hamsters were given subcutaneous injections of N-nitrosobis(2-oxopropyl)amine (BOP) 10 mg/kg body weight, every 2 weeks, four times. The animals were divided into three groups based on the simultaneous oral intake of a CE-2 pelleted diet, which contained 0% (group CE, n = 30), 0.01% (group ET, n = 21), or 0.04% Etodolac (group ET4, n = 25), respectively. Hamsters were killed for pathological examination 36 weeks after the operation. The incidence of induced pancreatic carcinoma was 93%, 81%, and 72% in groups CE, ET, and ET4, respectively. The pancreatic carcinomas were classified into four histological types: tubular, papillary, and cystic adenocarcinoma, and IPC. The incidence of IPC and the number of IPCs per animal were significantly lower in groups ET4 (36% and 0.48) and ET (48% and 0.62) than in group CE (67% and 1.30). The proliferating cell nuclear antigen labeling indices in the noncancerous epithelial cells of the main pancreatic duct were 2.8% and 6.8% in groups ET4 and ET, respectively; being significantly lower than that in group CE (10.8%). In conclusion, Etodolac inhibited BOP-induced IPC in hamsters. The suppression of epithelial cell proliferation of the main pancreatic duct was considered a possible mechanism of cancer prevention in this hamster model.
KeywordsProliferate Cell Nuclear Antigen Pancreatic Carcinoma Main Pancreatic Duct PGE2 Production Pancreatic Carcinogenesis
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