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Carcinogenesis Advance Access published online on June 8, 2005
Carcinogenesis, doi:10.1093/carcin/bgi149
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received January 7, 2005
Revised May 29, 2005
Accepted May 31, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Inhibitory effect of meloxicam, a cyclooxygenase-2 inhibitor, on N-nitrosobis (2-oxopropyl) amine induced biliary carcinogenesis in Syrian hamsters

Akihiko Tsuchida 1*, Takao Itoi 1, Kazuhiko Kasuya 1, Mitsufumi Endo 1, Kenji Katsumata 1, Toshiaki Aoki 1, Minako Suzuki 1, and Tatsuya Aoki 1

1 Third Department of Surgery, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

* To whom correspondence should be addressed.
Akihiko Tsuchida, E-mail: akibobo{at}hotmail.com


  Abstract

Pancreaticobiliary maljunction (PBM) is a high risk factor in biliary tract carcinoma. The chemopreventive action of a COX-2 inhibitor (meloxicam) on N-nitrosobis (2-oxopropyl) amine (BOP)-induced gallbladder cancer in hamster PBM models was investigated. In sevenweek-old female Syrian golden hamsters, the extrahepatic bile duct at the distal end of the common duct was ligated and cholecystoduodenostomy was performed (group I). In group II, the same surgery was performed and from week 4 after surgery, 10 mg/kg of BOP was injected subcutaneously once a week with a one-week interval. In group III, in addition to the measures employed in group II, 5 mg/kg/day of meloxicam was administered once a day, every week day. Pathological findings in the gallbladder on week 20 after surgery were as follows. In group I, proper epithelium was predominant and there was no cancer. In group II, proper epithelium was predominant, but there was also hyperplasia and atypical epithelium recognized in 8 of 11 cases (72.7%); the area of atypical epithelium was more extensive than that in group I. Carcinoma in situ (CIS) was recognized in 4 of 11 cases (36.4%) in group II. Group III showed the same pathological findings as group I. However, compared with group II, the incidence of atypical epithelium decreased to 27.3% and no cancerous lesion was observed. On week 20 after surgery, the PCNA labeling index in group III was statistically significantly lower than in group II (p=0.045). No statistically significant differences were noted among groups in terms of apoptosis labeling index on week 20 after surgery. In conclusion, it was confirmed that meloxicam suppresses carcinogenesis in hamster PBM models and its mechanism may be based on the suppression of cell growth.


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