ANTIPROLIFERATIVE EFFECTS OF THE ENANTIOMERS OF FLURBIPROFEN

Nonsteroidal antiinflammatory drugs (NSAIDs) are recognized for inhibi ting growth of colon tumors in animal models, and for reducing the ris k of colon cancer in humans. The mechanisms involved have not been est ablished, but are thought to be related to reduced prostaglandin biosy nthesis. The present study investigates the effect of COX-inhibiting a nd non-COX-inhibiting enantiomers of flurbiprofen on rat colonocyte pr oliferation, Intestinal ulceration was used as a surrogate indicator o f COX inhibition, Sprague Dawley rats were treated orally with 6.3 mg/ kg of R- or S-flurbiprofen or vehicle, Colonocyte labeling index and s mall bowel ulcer index were measured. R-flurbiprofen and S-flurbiprofe n significantly reduced colonocyte labeling index, by 34% and 23% resp ectively, compared with vehicle. R-flurbiprofen caused minimal ulcer f ormation (4.48 mm(2)) compared with S-flurbiprofen (94.4 mm(2)). These findings suggest that R-flurbiprofen-mediated control of colonocyte p roliferation is independent of prostaglandin biosynthesis.