Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells

AIM:To explore the synergistic effect of docosahexaenoic acid (DHA)/5-fluorouracil (5-FU) on the human gastric cancer cell line AGS and examine the underlying mechanism.METHODS: AGS cells were cultured and treated with a series of concentrations of DHA and 5-FU alone or in combination for 24 and 48 h.To investigate the synergistic effect of DHA and 5-FU on AGS cells, the inhibition of cell proliferation was determined by MTT assay and cell morphology.Flow cytometric analysis was also used to assess cell cycle distribution, and the expression of mitochondrial electron transfer chain complexes (METCs) Ⅰ, Ⅱ and Ⅴ in AGS cells was further determined by Western blot analysis.RESULTS: DHA and 5-FU alone or in combination could markedly suppress the proliferation of AGS cells in a significant time and dose-dependent manner.DHA markedly strengthened the antiproliferative effect of 5-FU, decreasing the IC50 by 3.56-2.15-foldin an apparent synergy.The morphological changes of the