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

J E Martin, Graeme Young, Richard Le Leu, Ying Hu

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)3581-3588
    Number of pages8
    JournalAnticancer Research
    Volume33
    Issue number9
    Publication statusPublished - Sep 2013

    Keywords

    • ACF
    • Apoptosis
    • Colon cancer
    • COX inhibition
    • NSAIDS
    • Prevention
    • Rat model

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