Inhibitory effects of selective cyclooxygenase-2 inhibitors, nimesulide and etodolac, on the development of squamous cell dysplasias and carcinomas of the tongue in rats initiated with 4-nitroquinoline 1-oxide

The present study was conducted to examine the effects of selective cyclooxygenase (COX)-2 inhibitors, nimesulide and etodolac, on early stages of tongue carcinogenesis due to 4-nitroquinoline 1-oxide(4-NQO). Fischer 344 rats, 6 weeks old, were given 15 ppm of 4-NQO in their drinking water for 8 weeks followed by diet containing either nimesulide or etodolac at the doses of 150 and 300 ppm for 16 weeks. Rats were sacrificed at 24 weeks and tongue lesions were histologically examined. Nimesulide dose-dependently reduced the incidence and multiplicity of squamous cell dysplasias and carcinomas (SCCs), with significance at the 300 ppm dose. This suppression was associated with an increased incidence and multiplicity of hyperplasias. Etodolac exhibited similar but less extensive suppressive effects. The results suggest that COX-2 is involved in the progression of hyperplasia to dysplasia and from dysplasia to SCCs.