ω-3 and ω-6 Polyunsaturated Fatty Acids Regulate the Proliferation, Invasion and Angiogenesis of Gastric Cancer Through COX/PGE Signaling Pathway

Abstract

BackgroundThis study aims to investigate the effects of ω-3, ω-6 polyunsaturated fatty acids (PUFAs), and their middle metabolites prostaglandin (PGE)2 and PGE3 on proliferation, invasion, and angiogenesis formation of gastric cancer cells and to explore associated mechanism.MethodsRT-PCR and ELISA were used to detect the expression of cyclooxygenase (COX)-1 and COX-2 in gastric cancer cell lines. The effect of ω-3, ω-6, PGE2, and PGE3 on the proliferation, invasion, and angiogenesis of gastric cancer cells were measured by cell proliferation, invasion, and angiogenesis assay in vitro. COX-2 small interfering RNA (siRNA) was transfected into gastric cancer cells, and the expression of COX-2 protein was detected by Western blot. COX-2 gene silencing influencing proliferation, invasion, and angiogenesis potential of gastric cancer cells was detected by WST-1, transwell chamber, and angiogenesis assay, respectively.ResultsCOX-2 was only expressed in MKN74 and MKN45 cells. In gastric cancer cell lines with positive COX-2 expression, ω-6 and PGE2 could significantly enhance the proliferation, invasion, and angiogenesis of gastric cancer cells, and after transfection with COX-2 siRNA, the effects of ω-6 and PGE2 on enhancing the proliferation, invasion, and angiogenesis of gastric cancer cells were significantly attenuated; ω-3 and PEG3 could inhibit the proliferation, invasion, and angiogenesis of gastric cancer cells. In gastric cancer cell lines with negative COX-2 expression, ω-6 and PGE2 had no significant effect on the proliferation, invasion, and angiogenesis of gastric cancer; ω-3 and PGE3 could significantly inhibit the proliferation, invasion, and angiogenesis of gastric cancer.Conclusionω-6 PUFAs reinforce the metastatic potential of gastric cancer cells via COX-2/PGE2; ω-3 PUFAs inhibit the metastatic potential of gastric cancer via COX-1/PGE3 signaling axis.