Experimental study on therapy for oral cancer by cyclooxygenase-2 inhibitors

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We analyzed the efficacy of selective cyclooxygense(COX)-2 inhibitors, nimesulide and etodolac, in the rat model of tongue carcinogenesis using 4-nitroquinoline 1-oxide(4-NQO) in order to evaluate their chemopreventive efficacy on human oral cancers and reported the suppressive effect of these inhibitors on the development of squamous cell carcinomas(SCCs) and squamous cell daplasias, putative preneoplastis lesions. The present study was conducted to elucidate the roles of COX-2 in rat tongue carcinogenesis. Rats were administered 4-NQO (25-35 ppm) for 12 weeks and then etodolac (150ppm and 300ppm) was given for 16 weeks. The effect of etodolac on the incidence of neoplastic and preneoplastic lesions and the immunohistochemical expression of COX-2 and inducible nitoric oxide synthase (iNOS) in these lesions were analyzed. Etodolac at the dose of 300ppm significantly suppressed the incidence of SCCs from 100% to 50% in parallel with the increase of the incidence of dysplasias. The size of SCCs was also decreased. These results indicate that etodolac suppressed the progression of dysplasias to SCCs and the proliferative potential of SCCs. Immunohistochemical study on the expression of COX-2 and iNOS revealed that etodolac had no effect on the expression of COX-2 or iNOS. From these results, it is considered that the suppressive effect of etodolac on the development of SCCs was not exerted by the inhibition of COX-2 protein expression but by the inhibition of the enzymatic activity of COX-2.