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© 1993 Oxford University Press

other

Chemoprevention of OH-BBN-induced bladder cancer in mice by piroxicam

Richard C. Moon 1 2, Gary J. Kelloff 3, Carol J. Detrisac 1, Vernon E. Steele 3, Cathy F. Thomas 1 and Caroline C. Sigman 4

1IIT Research Institute Chicago, IL 60616
3National Cancer Institute, Chemoprevention Branch Bethesda, MD 20892
4CCS Associates Palo Alto, CA 94301, USA

2To whom all correspondence should be addressed at present address: Specialized Cancer Center (M/C 820), College of Medicine, University of Illinois, Chicago, 840 South Wood Avenue, Chicago, IL 60612, USA

Piroxicam inhibited induction of transitional cell carcinoma in mouse urinary bladder by N-butyl-N-(4-hydroxybutyl)-nitrosamine. At 15 mg piroxicam/kg diet, tumor incidence was reduced 82% (P < 0.0001) compared with carcinogen controls. At 30 mg piroxicam/kg diet, tumor incidence was reduced 70% (P < 0.001). Results at the higher dose level suggested that piroxicam also may have inhibited invasion slightly. Combination treatment with 2-difluoromethylornithine (DFMO) or all-trans-N-(4-hydroxyphenyl)retin-amide (4-HPR) or both agents did not improve the chemopreventive potential of piroxicam. However, the three-agent combination of 30 mg piroxicam/kg, 1200 mg DFMO/kg and 313 mg 4-HPR/kg diet was highly effective. Tumor incidence was reduced 91% (P < 0.0001) compared with carcinogen controls. Unfortunately, the high efficacy was somewhat compromised by a significant decrease in survival and body weight gain in mice receiving the combination of agents compared with the carcinogen control.


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