Eicosanoid Production and Growth Regulation in Rat Intestinal Epithelial Cells

Abstract

The role of eicosanoids in regulating intestinal epithelial proliferation and differentiation is unknown. For years clinicians have been aware that patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are at increased risk for development of ulcérations in the gastroenteric tract. These drugs are potent inhibitors of cyclooxygenase. Recent clinical studies indicate that NSAIDs may also affect intestinal polyp formation and/or the development of colon cancer in humans (1–6). One study demonstrated that colon polyp size and number decreased significantly in familial adenomatous polyposis patients treated with sulindac [a pro-drug which is converted to a cyclooxygenase inhibitor in the liver and colon] (5). In epidemiologic studies, cyclooxygenase inhibitors (like aspirin) have been shown to decrease the relative rate of colon cancer by about 40–50% in humans (1–4). The mechanism by which NSAIDs cause either polyp regression or lower the relative rate of colon cancer is unknown. The precise relationship between eicosanoid metabolism, intestinal epithelial growth regulation and carcinogenesis is presently an area of active investigation (2). We have recently reported that a mitogen inducible cyclooxygenase gene is activated in intestinal epithelial cells treated with growth factors or tumor promoters (7).