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Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis.

Abstract

PURPOSE

To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumor growth and in its prevention.

RESULTS

The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (V) CEL reduced MDA formation in serum (p < 0.001) and liver (p < 0.05) and also showed a trend to reduction in kidney.

METHODS

Drug treatments were performed during the first 8 w, followed by 12 w for tumor expression/prevention, in the following groups: control-vehicle; carcinogen-0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL)-10 mg/kg/day and preventive CEL + BBN. The bladders were analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status.

CONCLUSIONS

Celecoxib has demonstrated an outstanding inhibitory effect on bladder cancer chemoprevention, which might be due to its expected anti-inflammatory actions, as well as by anti-proliferatory and antioxidant actions. This data supports a pivotal role of cancer chemoprevention strategies based on COX-2 inhibition.

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  • Authors

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    Source

    Cancer biology & therapy 8:17 2009 Sep pg 1615-22

    MeSH

    Animals
    Anticarcinogenic Agents
    Cell Growth Processes
    Cyclooxygenase 2 Inhibitors
    Inflammation
    Male
    Oxidative Stress
    Pyrazoles
    Rats
    Rats, Wistar
    Sulfonamides
    Urinary Bladder
    Urinary Bladder Neoplasms
    Urothelium

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    19571668

    Citation

    TY - JOUR T1 - Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis. AU - Parada,Belmiro, AU - Sereno,José, AU - Reis,Flávio, AU - Teixeira-Lemos,Edite, AU - Garrido,Patricia, AU - Pinto,Angela Filipa, AU - Cunha,Maria Fernanda, AU - Pinto,Rui, AU - Mota,Alfredo, AU - Figueiredo,Arnaldo, AU - Teixeira,Frederico, Y1 - 2009/09/07/ PY - 2009/9/7/aheadofprint PY - 2009/7/3/entrez PY - 2009/7/3/pubmed PY - 2010/2/13/medline SP - 1615 EP - 22 JF - Cancer biology & therapy JO - Cancer Biol. Ther. VL - 8 IS - 17 N2 - PURPOSE: To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumor growth and in its prevention. RESULTS: The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (V) CEL reduced MDA formation in serum (p < 0.001) and liver (p < 0.05) and also showed a trend to reduction in kidney. METHODS: Drug treatments were performed during the first 8 w, followed by 12 w for tumor expression/prevention, in the following groups: control-vehicle; carcinogen-0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL)-10 mg/kg/day and preventive CEL + BBN. The bladders were analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status. CONCLUSIONS: Celecoxib has demonstrated an outstanding inhibitory effect on bladder cancer chemoprevention, which might be due to its expected anti-inflammatory actions, as well as by anti-proliferatory and antioxidant actions. This data supports a pivotal role of cancer chemoprevention strategies based on COX-2 inhibition. SN - 1555-8576 UR - https://www.unboundmedicine.com/medline/citation/19571668/Anti_inflammatory_anti_proliferative_and_antioxidant_profiles_of_selective_cyclooxygenase_2_inhibition_as_chemoprevention_for_rat_bladder_carcinogenesis_ L2 - http://www.landesbioscience.com/journals/cbt/abstract.php?id=9199 ER -