Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis. Cancer biology & therapy [Cancer Biol Ther] Journal article | | Title | Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis. | | Author(s) | Parada B, Sereno J, Reis F, Teixeira-Lemos E, Garrido P, Pinto AF, Cunha MF, Pinto R, Mota A, Figueiredo A, Teixeira F | | Institution | Institute of Pharmacology & Experimental Therapeutics, IBILI, Medicine Faculty, Coimbra University and Department of Urology & Renal Transplantation, Coimbra University Hospital, Portugal. | | Source | Cancer Biol Ther 2009 Sep 7; 8(17) | | 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: (a) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (b) 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)); (c) 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; (d) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (e) 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 weeks, followed by 12 weeks 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 analysed 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19571668 |
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