Experimental study on chemoprevention of oral cancer by cyclooxygenase-2 inhibitor

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We analyzed the effect of a selective cyclooxygenase (COX)-2 inhibitors, etodolac, on the expression of COX-2 and receptor for advanced glycation end products (RAGE) in the rat model of tongue carcinogenesis using 4-nitroquinoline 1-oxide (4-NQO).Fischer 344 rats, 6-week-old, were administered 4-NQO (30ppm) for 12 weeks and then etodolac (150ppm and 300ppm) was given for 16 weeks. The lesions developed were histologically classified into hyperplasia, dysplaisa, pappiloma and squamous cell carcinoma (SCC).The incidence of SCC was decreased significantly by 300ppm etodolac. Immunohistochemically, COX-2 was positive for basal cells in hyperplasia and papilloma, and for basal cells, dysplastic cell and cancer cells in dysplasia and SCC. On the other hand, RAGE was weakly and moderately positive for granular cells in hyperplasia and papilloma, and positive for dysplastic cells and cancer cells in dysplasia and SCC. Etodolac did not decrease the expression of COX-2 in these lesions but decreased the expression of RAGE. The analysis of RAGE mRNA using RT-PCR revealed that RAGE mRNA was expressed in SCC and the treatment by etodolac decreased the expression.These results indicate that the expression of COX-2 and RAGE is closely related and the inhibitory effect by etodolac is associated with the decrease of RAGE mRNA expression in rat tongue carcinogenesis by 4-NQO.