Chemoprevention of OH-BBN-induced bladder cancer in mice by piroxicam.
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-difluoromethyl-ornithine (DFMO) or all-trans-N-(4-hydroxyphenyl)retinamide (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.
Moon
R C
RC
IIT Research Institute, Chicago, IL 60616.
Kelloff
G J
GJ
Detrisac
C J
CJ
Steele
V E
VE
Thomas
C F
CF
Sigman
C C
CC
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000517:prevention & control*; D004357:Drug Synergism; D000518:Eflornithine / Q000494:pharmacology; D017313:Fenretinide / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010894:Piroxicam / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
D010894:Piroxicam; D017313:Fenretinide; D002085:Butylhydroxybutylnitrosamine; D000518:Eflornithine