R-flurbiprofen suppresses distal nonmucin-producing colorectal tumors in azoxymethane-treated rats, without suppressing eicosanoid production

Jonathan Martin, Ying Hu, Richard Le Leu, Graeme Young

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    Toxicity and gastrointestinal side effects limits the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as agents to prevent colorectal cancer. These undesirable effects appear to be related to the inhibition of cyclooxygenase-associated pathways. Using the azoxymethane (AOM)-rat model of carcinogenesis, we aimed to test the potency of a low-toxicity R-flurbiprofen and whether NSAIDs have differing effects on regional tumor subtypes. Groups of 50 rats were gavaged 6 days a week with drug. After 1 and 2 wk on drug, rats were given intraperitoneal injection of AOM (15 mg/kg body wt). Groups were controls, sulindac (nonselective cyclooxygenase inhibitor) 5 and 20 mg/kg body wt per day, and R-flurbiprofen 30 mg/kg body wt per day. Tumor location, size, and histological subtype (either mucinous or nonmucinous) were recorded after 30 wk. The incidence of colon tumors was significantly reduced in the sulindac 20 mg (P < 0.001) and the R-flurbiprofen groups (P < 0.03) compared with the control group. The sulindac 20 mg and R-flurbiprofen groups also showed a reduced number of distal colon tumors (P < 0.03), whereas proximal tumors were not affected. Tumors only of the nonmucinous subtype were significantly reduced with the sulindac 20 mg and R-flurbiprofen groups (P < 0.001). Tumor size was not significantly different between all groups. Only the sulindac 20 mg group showed a reduced colonic prostaglandin E2 concentration. The sulindac groups showed a dose-dependant reduction in body weight gain (P < 0.001). In conclusion, R-flurbiprofen at a dose of 30 mg/kg body wt per day was well tolerated by the animals and, along with sulindac at 30 mg/day body wt, showed protection against the development of colon cancer in the rat-AOM model.

    Original languageEnglish
    Pages (from-to)G860-G864
    Number of pages5
    JournalAmerican Journal of Physiology-Gastrointestinal and Liver Physiology
    Volume298
    Issue number6
    DOIs
    Publication statusPublished - Jun 2010

    Keywords

    • Colon cancer
    • Nonsteroidal anti-inflammatory drugs
    • Sulindac

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