SELECTIVE PRESERVATION OF PROTEIN-KINASE C-ZETA IN THE CHEMOPREVENTION OF AZOXYMETHANE-INDUCED COLONIC TUMORS BY PIROXICAM

While nonsteroidal anti-inflammatory drugs have been shown to exert pr eventive effects against the development of colonic tumors in humans a nd in chemically-induced tumors in animal models, the mechanism(s) inv olved in this phenomenon is unclear. We have recently demonstrated tha t one such agent, piroxicam, when supplemented (75 ppm) in the diets o f rats administered azoxymethane, reduced the incidence of rats bearin g tumors. To date, the effects of piroxicam on protein kinase C, a fam ily of serine/threonine kinases which may be intimately involved in th e colonic malignant transformation process, have not been examined. It was, therefore, of interest to determine whether piroxicam altered th e expression of one or more isoforms of this kinase in these tumors. T he present studies demonstrate that dietary piroxicam selectively pres erved the expression of protein kinase C-Sin azoxymethane-induced tumo rs; suggesting that this is at least one mechanism involved in this ag ent's chemopreventive actions in this organ.