NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND TUMOR PROGRESSION - INHIBITION OF FIBROBLAST HYALURONIC-ACID PRODUCTION BY INDOMETHACIN AND MEFENAMIC-ACID

The antitumor effects of non-steroidal anti-inflammatory drugs (NSAIDs ) have been documented in a variety of both clinical and experimental settings, although the mechanisms responsible remain unclear. In the p resent study, we show that the NSAIDs indomethacin and mefenamic acid inhibit the calf serum-stimulated production of hyaluronic acid (HA) i n murine Swiss 3T3 fibroblasts, at concentrations where DNA synthesis is unaffected. HA is an extracellular matrix glycosaminoglycan associa ted with cell migration and tumor invasion. Our data suggest that one mechanism whereby NSAIDs inhibit tumor progression may be to inhibit t he synthesis of HA by host fibroblasts, and that the eicosenoid pathwa y may represent an important control point in the growth-factor-mediat ed production of HA in fibroblasts. Thus the use of an agent which inh ibits HA synthesis may be a novel approach to alter the invasive and m etastatic properties of tumor cells in a non-cytotoxic fashion.