GLA synergistic with gemcitabine in pancreatic cancer




Pancreatology. 2003;3(5):367-73; discussion 373-4. Epub 2003 Sep 24.

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

Whitehouse PA, Cooper AJ, Johnson CD.

Department of Surgery, Southampton General Hospital, Southampton, UK.

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 microg/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 microg/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 2003
S. Karger AG, Basel and IAP