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

作者：Parada Belmiro; Sereno Jose; Reis Flavio; Teixeira Lemos Edite; Garrido Patricia; Pinto Angela Filipa; Cunha Maria Fernanda; Pinto Rui; Mota Alfredo; Figueiredo Arnaldo; Teixeira Frederico^*

来源：Cancer Biology and Therapy, 2009, 8(17): 1622-1629.

DOI：10.4161/cbt.8.17.9199

• bladder cancer
• chemoprevention
• cyclooxygenase-2 inhibition
• inflammation
• proliferation
• oxidative stress
• rat model

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 TGF beta 1 and CRP and increase TNF alpha and IL-1 beta (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.

• 出版日期2009-9-1