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

Jiachi Ma,Wanqing Liang,Lei Li,Jun Du,Chensong Zhang,Yuzhong Chen,Bangling Chen,Chengwu Pan,Yuanpeng Wang

doi:10.3389/fonc.2022.802009

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.

Highlights

Gastric cancer is one of the common malignant tumors, with an incidence of 17.6/100,000 worldwide, about 1.1 million new cases per year, accounting for 5.6% of all new cases of malignant tumors and ranking fifth, and it ranks fourth due to 770,000 deaths it causes [1]
The w-3 and w-6 polyunsaturated fats are the most common polyunsaturated fats. They play an indispensable role in maintaining the normal physiological metabolism of the human body and are essential fatty acids for the human body
While w-3 Polyunsaturated fatty acids (PUFAs) produce prostaglandin E3 (PGE3) after binding to cyclooxygenase 1 (COX-1), PGE3 can inhibit the production of PGE2 and can inhibit phospholipase A2 (PLA2), phosphatidylinositol-specific phospholipase C (PI-PLC), nuclear factor-kB, and cyclooxygenase 2 (COX-2) activities, which in turn reduce the proliferation and invasion w-3 and w-6 Regulate Metastasis in Gastric Cancer of tumor cells and play a role in inhibiting the growth and metastasis of malignant tumors [8, 12, 19–21]

Summary

Introduction

Gastric cancer is one of the common malignant tumors, with an incidence of 17.6/100,000 worldwide, about 1.1 million new cases per year, accounting for 5.6% of all new cases of malignant tumors and ranking fifth, and it ranks fourth due to 770,000 deaths it causes [1]. Polyunsaturated fatty acids (PUFAs) w-3 and w-6 are the main components of cell membrane structure, which are essential fatty acids for human body. The applicant’s previous studies have shown that, PUFAs can affect the invasion, proliferation, and angiogenesis of gastric cancer cells, and the role of PUFAs is closely related to their metabolites prostaglandin (PGE) and cyclooxygenase (COX) on the nuclear membrane of tumor cells in vivo, while the expression of PGE and COX is closely related to lymphatic metastasis of gastric cancer [11]. This study aims to investigate the effects of w-3, w-6 polyunsaturated fatty acids (PUFAs), and their middle metabolites prostaglandin (PGE) and PGE3 on proliferation, invasion, and angiogenesis formation of gastric cancer cells and to explore associated mechanism

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Results

Conclusion