Synergistic activity of gamma-linolenic acid and cytotoxic drugs against pancreatic adenocarcinoma cell lines

Background: gamma-Linolenic acid (GLA) is growth inhibitory both in vitro and in vivo, at doses non-toxic to non-cancer cells. Chemotherapeutic agents have limited activity in pancreatic cancer. Interactions between GLA and cytotoxic drugs have not previously been investigated; any synergy might improve the therapeutic effect of these agents. Aim: To investigate possible interactions between GLA and 5-fluorouracil (5-FU) or gemcitabine against pancreatic cancer cell lines in vitro. Methods: Two pancreatic cancer cell lines were exposed to GLA alone and in combination with 5-FU or gemcitabine. Residual viable biomass was measured using the MTT assay and the results analysed by the median effect method of Chou and Talalay [Adv Enzyme Regul 1984; 22: 27-55]. Results: GLA concentrations of 3.9-125 mug/ml had a synergistic or additive growth inhibitory effect on all tested concentrations of gemcitabine. Synergism was demonstrated between GLA and 5-FU only at concentrations of 62.5-125 mug/ml of 5-FU. Conclusion: GLA has a synergistic effect with gemcitabine at concentrations that correspond to in vivo therapeutic doses. GLA with 5-FU is synergistic only at a tight range of high concentrations of 5-FU. GLA lacks toxic side effects and may be useful in combination with gemcitabine. Copyright (C) 2003 S. Karger AG, Basel and IAP.