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Chemopreventive Effects of Nimesulide, a Selective Cyclooxygenase-2 Inhibitor, on the Development of Rat Urinary Bladder Carcinomas Initiated by N-Butyl-N-(4-hydroxybutyl)nitrosamine¹

Department of Oncological Pathology, Cancer Center [E. O., A. D., M. T., H. A., Y. S., W. K., Y. K.], and Department of Urology [E. O., S. O.], Nara Medical University, Nara 634; and Cancer Prevention Division, National Cancer Center Research Institute [K. W.], Tokyo 104, Japan

The chemopreventive potential of a selective cyclooxygenase-2 inhibitor, nimesulide (NIM), against the development of rat superficial urinary bladder carcinomas after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Six-week-old Fischer 344 male rats were given 0.05% BBN in their drinking water for 8 weeks, followed by diets supplemented with 0, 100, 200, or 400 ppm NIM for 12 weeks, and they were then sacrificed. NIM decreased, in a dose-dependent manner, the incidence of transitional cell carcinoma (TCC) to 12 of 20 (60.0%), 8 of 16 (50.0%), and 5 of 19 (26.3%) and the multiplicity of TCCs to 0.75 ± 0.79, 0.56 ± 0.63, and 0.37 ± 0.78 per rat at 100, 200, and 400 ppm, respectively, as compared with the BBN alone group values of 18 of 20 (90.0%) and 2.35 ± 1.23. NIM did not significantly affect the cell differentiation or invasiveness of TCCs. These results indicate clear chemopreventive potential of a selective cyclooxygenase-2 inhibitor against postinitiation development of superficial rat urinary bladder carcinomas.

¹ This work was supported in part by Grant-in Aid 09253104 for Cancer Research from the Ministry of Education, Science and Culture; a Grant-in Aid from the Ministry of Health and Welfare for the Second-Term Comprehensive 10-Year Strategy for Cancer Control, Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation; and a grant from the Program for Promotion of Fundamental Studies in Health Sciences of the Organisation for Drug ADR Relief, R&G Promotion and Product Review of Japan.

² To whom requests for reprints should be addressed, at Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634, Japan.

Received 10/ 9/97. Accepted 5/18/98.

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