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Type: Journal article
Title: Comparing the effects of COX and Non-COX-inhibiting NSAIDs on enhancement of apoptosis and inhibition of aberrant crypt foci formation in a rat colorectal cancer model
Author: Martin, J.
Young, G.
Le Leu, R.
Hu, Y.
Citation: Anticancer Research: international journal of cancer research and treatment, 2013; 33(9):3581-3588
Publisher: International Institute of Anticancer Research
Issue Date: 2013
ISSN: 0250-7005
Statement of
Jonathan E. Martin, Graeme P. Young, Richard K. Le Leu and Ying Hu
Abstract: The protection against colorectal cancer (CRC) by non-steroidal anti-inflammatory drugs (NSAIDs) is in part dependent on inhibition of cyclooxygenase (COX). We compared the efficacy of the non-COX-inhibiting R-flurbiprofen (R-FB) with COX-inhibiting sulindac and racemic flurbiprofen (Rac-FB), and determined their effects on apoptosis, in an azoxymethane (AOM)-induced rat CRC model. In experiment 1, groups of rats were given a daily drug gavage (R-FB 30 mg/kg, Rac-FB 10 mg/kg and Sulindac 20 mg/kg) for one week, followed by AOM treatment and were sacrificed eight hours later, colons were examined for apoptosis and cell proliferation. In experiment 2, groups of rats were given two AOM treatments, followed by a daily drug gavage until they were sacrificed ten weeks later, and colons were examined for aberrant crypt foci (ACF) and prostaglandin E2 production. All drugs significantly enhanced apoptosis and inhibited ACF, irrespective of their COX-inhibiting potency (p<0.01), but sulindac was more potent in inhibition of large ACF, p<0.05. COX-inhibiting sulindac achieved the greatest protective effect. The greater safety profile of Rac-FB should provide an advantage for chemoprevention.
Keywords: NSAIDS; colon cancer; prevention; COX inhibition; apoptosis; ACF; rat model
Rights: Copyright© 2013 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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