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Increased Expression of Cyclooxygenase-2 Protein in 4-Nitroquinoline-1-oxide-induced Rat Tongue Carcinomas and Chemopreventive Efficacy of a Specific Inhibitor, Nimesulide¹

Departments of Oncological Pathology [H. S., A. D., W. K., Y. S., M. T., Y. K.], and of Oral and Maxillofacial Surgery [H. S., K. Y., T. E., M. S.], Nara Medical University, Kashihara, Nara 634-8521, Japan

Expression of cyclooxygenase (COX)-2 protein in 4-nitroquinoline-1-oxide (4-NQO)-induced rat tongue lesions and the postinitiation chemopreventive potential of a selective COX-2 inhibitor, nimesulide (NIM), were examined in Fischer 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 drinking water for 12 weeks. Western blot analysis revealed COX-2 protein to be barely expressed in the normal tongue epithelia, whereas it was increased 6-fold in squamous cell carcinomas (SCCs). Immunohistochemically, COX-2 protein was diffusely present in SCCs and dysplasia but expressed only in basal cells in hyperplasia and papillomas. In basal cells of normal epithelia, it was also occasionally weakly stained. NIM dose-dependently decreased 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 of 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 significantly affect the development of hyperplasias, dysplasias, and papillomas. These results clearly indicate chemopreventive potential of a selective COX-2 inhibitor against the postinitiation development of SCCs in rat tongue carcinogenesis.

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