Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and β-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment

The effects of the non-steroidal anti-inflammatory drug (NSAID) piroxicam and the carotenoids lycopene and β-carotene, alone or in combination, on the development of rat superficial urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats, 6 weeks old, were given 0.05% BBN in the drinking water for 8 weeks followed by administration of piroxicam (0.0075% in the diet), lycopene (0.0025% in the drinking water) and/or β-carotene (0.0025% in the drinking water) for 12 weeks, then killed for histological analysis of urinary bladder lesions. Cell proliferation potential was analyzed by immunohistochemical staining of the proliferative cell nuclear antigen (PCNA). Piroxicam alone, piroxicam + lycopene, and piroxicam + lycopene + β-carotene all significantly decreased the incidences and numbers of transitional cell carcinomas (TCCs), but the combination of piroxicam with carotenoids did not result in a clear improvement in the preventive potential of piroxicam. Piroxicam + β-carotene also caused a significant reduction and lycopene alone a slight but not significant reduction in the number of TCCs. In contrast, β-carotene alone and lycopene + β-carotene were without inhibitory influence on any of the lesion categories examined, and the latter significantly increased the proportion of high-grade TCCs. Nevertheless, all of the chemopreventive agents, either alone or in combination, significantly decreased the TCC PCNA index, the effect extending to the surrounding epithelium in the piroxicam + lycopene and piroxicam + lycopene + β-carotene groups. These results indicate that the NSAID piroxicam may be a more effective chemopreventive agent than lycopene and β-carotene for superficial urinary bladder carcinogenesis.