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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.

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  • Authors+Show Affiliations

    ,

    Institute of Pharmacology & Experimental Therapeutics, IBILI, Medicine Faculty, Sub-Unit 1 (Polo III), Coimbra University, 3000-354 Coimbra, Portugal.

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    Source

    Mediators of inflammation 2010: 2010 pg 380937

    MeSH

    Animals
    Anticarcinogenic Agents
    Butylhydroxybutylnitrosamine
    Celecoxib
    Cyclooxygenase 2 Inhibitors
    Disease Models, Animal
    Inflammation Mediators
    Kidney
    Liver
    Male
    Oxidation-Reduction
    Pyrazoles
    Rats
    Rats, Wistar
    Sulfonamides
    Urinary Bladder Neoplasms

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    21403827

    Citation

    TY - JOUR T1 - Preventive but not curative efficacy of celecoxib on bladder carcinogenesis in a rat model. AU - Sereno,José, AU - Parada,Belmiro, AU - Reis,Flávio, AU - Cunha,Fernanda X, AU - Teixeira-Lemos,Edite, AU - Garrido,Patrícia, AU - Pinto,Rui, AU - Rocha-Pereira,Petronila, AU - Neto,Paula, AU - Ruivo,José, AU - Rodrigues-Santos,Paulo, AU - Nunes,Sara, AU - Mota,Alfredo, AU - Figueiredo,Arnaldo, AU - Teixeira,Frederico, Y1 - 2011/02/13/ PY - 2010/07/29/received PY - 2010/10/23/revised PY - 2010/12/02/accepted PY - 2011/3/16/entrez PY - 2010/1/1/pubmed PY - 2011/7/9/medline SP - 380937 EP - 380937 JF - Mediators of inflammation JO - Mediators Inflamm. VL - 2010 N2 - 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. SN - 1466-1861 UR - https://www.unboundmedicine.com/medline/citation/21403827/Preventive_but_not_curative_efficacy_of_celecoxib_on_bladder_carcinogenesis_in_a_rat_model_ L2 - https://dx.doi.org/10.1155/2010/380937 ER -