Journal Article

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

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

in Carcinogenesis

Volume 26, issue 11, pages 1922-1928
Published in print November 2005 | ISSN: 0143-3334
Published online June 2005 | e-ISSN: 1460-2180 | DOI:
Inhibitory effect of meloxicam, a cyclooxygenase-2 inhibitor, on N-nitrosobis (2-oxopropyl) amine induced biliary carcinogenesis in Syrian hamsters

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Pancreaticobiliary maljunction (PBM) is a high risk factor in biliary tract carcinoma. The chemopreventive action of a cyclooxygenase (COX)-2 inhibitor (meloxicam) on N-nitrosobis (2-oxopropyl) amine (BOP)-induced gallbladder cancer in hamster PBM models was investigated. In 7-week-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 1-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 weekday. Pathological findings in the gallbladder in week 20 after surgery were as follows. In group I, proper epithelium (PE) was predominant and there was no cancer. In group II, PE was predominant, but there was also hyperplasia and atypical epithelium (AE) recognized in 8 of 11 cases (72.7%); the area of AE 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 AE decreased to 27.3% and no cancerous lesion was observed. In week 20 after surgery, the proliferative cell nuclear antigen labeling index in group III was statistically significantly lower than in group II (P = 0.045). No statistically significant differences were noted among the groups in terms of apoptosis labeling index in 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.

Keywords: AE, atypical epithelium; ApoLI, apoptosis labeling index; BOP, N-nitrosobis (2-oxopropyl) amine; CD, cholecystoduodenostomy; CIS, carcinoma in situ; COX, cyclooxygenase; HE, hyperplastic epithelium; LI, labeling index; ME, metaplastic epithelium; NSAIDs, non-steroidal anti-inflammatory drugs; PBM, pancreaticobiliary maljunction; PCNA, proliferative cell nuclear antigen; PE, proper epithelium; PG, prostaglandin; PGE2, prostaglandin E2

Journal Article.  5095 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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