The research on chemoprevention and therapy for oral cancer by selective inhibitors of cyclooxygenase-2

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The expression of cyclooxygenase (COX)-2 is elevated in various cancer and considered to be related to carcinogen sis. We analyzed the expression of COX-2 protein in the tongue lesions induced by 4-nitroquinoline 1-oxide (4-NQO) in rats and the inhibitory efficacy of selective inhibitors, nimesulide (NIM) and etodolac. The lesions induced by 4-NQO are classified into hyperplasias, dysphasias, papillomas and squamous cell carcinomas (SCCs). The immunohistochemical expression of COX-2 protein is elevated especially in dysplasias and carcinomas. Western blot analysis showed 6-fold increase of COX-2 protein level in SCCs compared with normal epithelium. The administration of NIM and etodolac after initiation phase by 4-NQO decreased the incidences and multiplicities of SCCs dose-dependently. But, the incidences of dysphasia's, putative preneoplastic lesions, did not decreased. Then, we analyzed the effect of NIM and etodolac in the initiation phase of tongue carcinogensis by 4-NQO. The incidence of dysphasia's decreased dose-dependently. From the results described above, in rat tongue carcinogen sis, COX-2 protein level increases in dysphasia's and SCCs, and NIM and etodolac inhibit the development of dysphasia's and the progression to SCCs. Therefore, selective COX-2 inhibitors can be chemo preventive medicines for human oral cancer.