Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specificinhibitor, nimesulide

Expression of cyclooxygenase (COX)-2 protein in 4-nitroquinoline-loxide (4- NQO)-induced rat tongue lesions and the postinitiation chemopreventive pote ntial of a selective COX-2 inhibitor, nimesulide (NIM), were examined in Fi scher 344 male rats. NIM was administered in the diet at doses of 150, 300, and 600 ppm for 14 weeks after treatment with 25-35 ppm 4-NQO in the drink ing water for 12 weeks. Western blot analysis revealed COX-2 protein to be barely expressed in the normal tongue epithelia, whereas it was increased s imilar to6-fold in squamous cell carcinomas (SCCs). Immunohistochemically, COX-2 protein was diffusely present in SCCs and dysplasia but expressed onl y in basal cells in hyperplasia and papillomas. In basal cells of normal ep ithelia, it was also occasionally weakly stained. NIM dose-dependently decr eased at doses of 150 and 300 ppm, the incidences of SCCs to 4 of 12 (33.3% ) and 1 of 13 (7.7%) and their multiplicity to 0.33 +/- 0.49 and 0.08 +/- 0 .28 per rat, respectively, as compared with 4-NQO alone group values of 9 o f 11 (81.8%) and 1.00 +/- 0.77. A lesser decrease was observed with 600 ppm , the values being 5 of 12 (41.7%) and 0.50 +/- 0.67. NIM did not significa ntly affect the development of hyperplasias! dysplasias, and papillomas. Th ese results clearly indicate chemopreventive potential of a selective COX-2 inhibitor against the postinitiation development of SCCs in rat tongue car cinogenesis.