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.


OBJECTIVE
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.


CONCLUSIONS
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.
Whitehouse
P A
PA
Department of Surgery, Southampton General Hospital, Southampton, UK.
Cooper
A J
AJ
Johnson
C D
CD
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D017965:gamma-Linolenic Acid / Q000494:pharmacology*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D017965:gamma-Linolenic Acid; D005472:Fluorouracil; D000093542:Gemcitabine