title: Preventive but not curative efficacy of celecoxib on bladder carcinogenesis in a rat model.
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.
authors.affiliation: Institute of Pharmacology & Experimental Therapeutics, IBILI, Medicine Faculty, Sub-Unit 1 (Polo III), Coimbra University, 3000-354 Coimbra, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Sereno
authors.forename: Belmiro
authors.initials: B
authors.lastname: Parada
authors.forename: Flávio
authors.initials: F
authors.lastname: Reis
authors.forename: Fernanda X
authors.initials: FX
authors.lastname: Cunha
authors.forename: Edite
authors.initials: E
authors.lastname: Teixeira-Lemos
authors.forename: Patrícia
authors.initials: P
authors.lastname: Garrido
authors.forename: Rui
authors.initials: R
authors.lastname: Pinto
authors.forename: Petronila
authors.initials: P
authors.lastname: Rocha-Pereira
authors.forename: Paula
authors.initials: P
authors.lastname: Neto
authors.forename: José
authors.initials: J
authors.lastname: Ruivo
authors.forename: Paulo
authors.initials: P
authors.lastname: Rodrigues-Santos
authors.forename: Sara
authors.initials: S
authors.lastname: Nunes
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Figueiredo
authors.forename: Frederico
authors.initials: F
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*
chemical_list: D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D018836:Inflammation Mediators; D011720:Pyrazoles; D013449:Sulfonamides; D002085:Butylhydroxybutylnitrosamine; D000068579:Celecoxib