Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2010 (2010), Article ID 380937, 11 pages
http://dx.doi.org/10.1155/2010/380937
Research Article

Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

1Institute of Pharmacology & Experimental Therapeutics, IBILI, Medicine Faculty, Sub-Unit 1 (Polo III), Coimbra University, 3000-354 Coimbra, Portugal
2Department of Urology & Renal Transplantation, Coimbra University Hospital, 3000-075 Coimbra, Portugal
3Institute for Molecular and Cellular Biology, Porto University, 4150 Porto, Portugal
4Service of Anatomic Pathology, Coimbra University Hospital, 3000-075 Coimbra, Portugal
5Pharmacology & Pharmacotoxicology Unit, Pharmacy School of Lisbon, 1649-003 Lisboa, Portugal
6Research Centre for Health Sciences, Beira Interior University, 6201-001 Covilhã, Portugal
7Immunology & Oncology Laboratory, Centre for Neuroscience and Cell Biology, 3004-517 Coimbra, Portugal

Received 29 July 2010; Revised 23 October 2010; Accepted 2 December 2010

Academic Editor: Fulvio D'Acquisto

Copyright © 2010 José Sereno et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL), on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P), and curative CEL (BBN+CEL-C) groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%), BBN 13/20(65%), CEL 0/8(0%), CEL+BBN-P 1/8(12.5%), and BBN+CEL-C 6/8(75%). The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.