Prevention by nimesulide of N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters

A. Nishikawa, MD, PhD a, F. Furukawa, PhD a, K. Okazaki, MS a, T. Umemura, DVM, PhD a, K. Wakabayashi, PhD b and M. Hirose, MD, PhD a

a Division of Pathology, National Institute of Health Sciences; b Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan

[AIM] Because the vast majority of pancreatic cancer cases have been incurable at the time of diagnosis, early detection and prevention offer the only hope for effective control of this disease. Recent studies suggest that COX-2 is closely associated with the growth and progression of human cancers in various organs such as the colon, stomach, liver, lung and pancreas. Therefore, the modification effects of nimesulide, a COX-2 inhibitor, administration during the post-initiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl) amine (BOP). [METHODS] Male Syrian hamsters were given four weekly sc injections of BOP at a dose of 10 mg/kg and thereafter they were administered 0, 100 or 400 ppm nimesulide in the diet for 36 weeks. Additional groups of hamsters were fed 400 ppm nimesulide without prior BOP-initiation or non-treated. At week 40 of the experiment, all surviving animals were sacrificed, and development of neoplastic and preneoplastic lesions was assessed histopathologically. [RESULTS] The incidence of pancreatic adenocarcinomas was significantly (p<0.05) decreased in the BOP/400 ppm nimesulide group as compared to the BOP alone group. The multiplicity of total lesions of pancreatic adenocarcinomas plus atypical hyperplasias was also significantly (p<0.05) lowered. Immunohistochemically, COX-2 was overexpressed in pancreatic adenocarcinoma cells, showing a tendency for decrease by the nimesulide treatment. The incidence and multiplicity of neoplastic lesions in other organs did not significantly differ among the BOP-treated groups. No neoplastic lesions were detected in animals receiving nimesulide alone. [CONCLUSION] Our results clearly indicate that nimesulide protects against BOP-induced pancreatic tumors in hamsters.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prevention.