Polyunsaturated fatty acids augment tumoricidal action of 5-fluorouracil on gastric cancer cells by their action on vascular endothelial growth factor, tumor necrosis factor-α and lipid metabolism related factors

INTRODUCTION: Gastric cancer is the second most common cause of cancer-related mortality worldwide. 5-fluorouracil (5-FU) is a commonly used anti-cancer drug. Various polyunsaturated fatty acids (PUFAs) are known to have tumoricidal action both in vitro and in vivo. Though PUFAs are known to augment the cytotoxic action of anti-cancer drugs, the exact mechanism is not clear. MATERIAL AND METHODS: The human gastric cancer cell line MGC (undifferentiated) and human gastric cancer cell line SGC (semi-differentiated) were either 5-FU alone or a combination of 5-FU + PUFAs and their proliferation, and ability to secrete tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) and lipid metabolism-related factors lipoprotein lipase (LPL), peroxisome proliferator-activated-γ (PPAR-γ), and CCAAT enhancer-binding protein (C/EBP) were investigated and analyzed. RESULTS: It was noted that combined treatment of 5-FU + PUFAs on gastric carcinoma (MGC and SGC) cells produced a significant growth inhibitory action compared with either agent alone by inhibiting the production of TNF-α and VEGF and a simultaneous increase in the expression of LPL, PPAR-γ, and C/EBP. CONCLUSIONS: Based on the results of the present study, it is concluded that PUFAs enhance the tumoricidal action of the anti-cancer drug 5-FU by acting on anti-angiogenic factors and enzymes involved in lipid metabolism.