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Carcinogenesis Advance Access published online on February 21, 2008
Carcinogenesis, doi:10.1093/carcin/bgn047
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Chemopreventive effects of a selective cyclooxygenase-2 inhibitor (Etodolac) on chemically induced intraductal papillary carcinoma of the pancreas in hamsters

Tomohiko Adachi, M.D., Yoshitsugu Tajima, M.D., Ph.D., Tamotsu Kuroki, M.D., Ph.D., Takehiro Mishima, M.D., Amane Kitasato, M.D., Noritsugu Tsuneoka, M.D., Ph.D. and Takashi Kanematsu, M.D., Ph.D.

Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences

Correspondence to Tomohiko Adachi, M.D., Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan, Tel: 95849-7316, Fax: 95849-7319, E-mail address: adatomo{at}nifty.com

The present study was designed to determine whether 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 received subcutaneous injections of N-nitrosobis(2-oxopropyl)amine (BOP) 4 times at a dose of 10 mg/kg body weight, every 2 weeks. The animals were divided into 3 groups according to the simultaneous oral intake of a standard pelleted diet containing Etodolac at 0% (group CE, n=30), 0.01% (group ET, n=21), and 0.04% (group ET4, n=25), respectively. Hamsters were killed for pathological examination at 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 histologically classified into 4 types, i.e., tubular, papillary, and cyst 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) when compared to 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, and were significantly lower than that in group CE (10.8%). In conclusion, Etodolac inhibited BOP-induced IPC in hamsters. Suppression of epithelial cell proliferation of the main pancreatic duct was considered as a possible mechanism of cancer prevention in this hamster model.

Key Words: intraductal papillary mucinous neoplasm • intraductal papillary carcinoma • cyclooxygenase-2 inhibitor • chemoprevention • hamster

Received September 17, 2007; revised January 8, 2008; accepted February 4, 2008.


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