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. 1. Introduction Bladder cancer is a prevalent tumor, accounting for 5%–10% of all malignancies in Western countries [1, 2]. It has a high recurrence and progression rate and the prognosis, except for superficial forms, is poor . Furthermore, it has high mortality rates and socioeconomic costs [4, 5]. The conventional surgical techniques and therapeutic options might cause discomfort to patients, especially in invasive and aggressive forms of cancer [6, 7]. Therefore, the improvement of bladder cancer management and treatment could rely on better preventive strategies. The identification of promising drugs remains dependent on a better elucidation of the molecular/cellular mechanisms underlying cancer appearance and progression [8, 9]. Apart from the genetic features and markers already characterized [10, 11], the cellular and molecular mechanisms for development and/or progression might involve inflammatory, proliferative, and oxidative stress phenomena that should be better elucidated. Inflammation through the cyclooxygenase (COX) pathway has been involved in cancer development . While COX-1 is constitutively expressed in a huge range of tissues, playing a role in
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