Polyunsaturated Fatty Acids ω-3 and ω-6 Regulate the Proliferation Invasion and Angiogenesis of Human Gastric Cancer Through COX/PGE Signaling Pathway
Abstract Background: To investigate the effect of polyunsaturated fatty acids ω-3 and ω-6 and their metabolites prostaglandin PGE2 and PGE3 on the proliferation, invasion and neovascularization of gastric cancer.Methods: RT-PCR and ELISA were used to detect the gene and protein expression of COX-1 and COX-2 in gastric cancer cell lines, respectively. The effects of ω-3, ω-6, PFG2 and PEG3 on the proliferation, invasion and neovascularization of gastric cancer cells were detected by cell proliferation, invasion and neovascularization assay in vitro. COX-2 siRNA was synthesized by short gene interfering RNA (siRNA) technique and transfected into gastric cancer cells, and the expression of COX-2 protein in gastric cancer cell lines was detected again by Western blot. The effects of COX-2 gene silencing on proliferation, invasion and neovascularization of gastric cancer cells were detected by WST-1 assay, transwell chamber assay and gastric cancer neovascularization assay, respectively.Results: COX-2 was only expressed in MKN74 and MKN45 cell lines, while COX-1 was expressed in four gastric cancer cell lines. In gastric cancer cell lines with positive COX-2 expression, ω-6 and PEG2 could significantly enhance the proliferation, invasion and neovascularization of gastric cancer cells, and after transfection with COX-2 siRNA, the effects of ω-6 and PEG2 on enhancing the proliferation, invasion and neovascularization of gastric cancer cells were significantly attenuated; ω-3 and PEG3 could inhibit the proliferation, invasion and neovascularization of gastric cancer cells. In gastric cancer cell lines with negative COX-2 expression, ω-6 and PEG2 had no significant effect on the proliferation, invasion and neovascularization of gastric cancer; ω-3 and PEG3 could significantly inhibit the proliferation, invasion and neovascularization of gastric cancer.Conclusion: ω-6 PUFAs reinforce the metastatic potential energy of gastric cancer cells via COX-2/PGE2; ω-3 PUFAs inhibit the metastatic potential energy of gastric cancer via COX-1/PGE3.