G Protein–Coupled Receptor 30 Mediates the Anticancer Effects Induced by Eicosapentaenoic Acid in Ovarian Cancer Cells
| Autor: | Cong-Jian Xu, Tian-Yu Wu, Jing-Mei Wang, Meng-Fei Zhao, Chao-Jun Li, Mei-Lin Yang, Yue Zhao, Xi Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway GPR30 Cancer Research Eicosapentaenoic acid Mice Nude Apoptosis Receptors G-Protein-Coupled Mice 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor Tumor Cells Cultured Animals Humans Medicine Protein kinase A signaling Receptor Protein kinase B health care economics and organizations Cell proliferation Ovarian Neoplasms Cell growth business.industry Cell Cycle Prognosis medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology Receptors Estrogen Oncology 030220 oncology & carcinogenesis Cancer research Female Original Article lipids (amino acids peptides and proteins) business Ovarian cancer Adenocarcinoma Clear Cell |
| Zdroj: | Cancer Research and Treatment : Official Journal of Korean Cancer Association |
| ISSN: | 2005-9256 1598-2998 |
| DOI: | 10.4143/crt.2019.380 |
| Popis: | PurposeWhile numerous epidemiological studies have indicated that omega-3 polyunsaturated fatty acids have anticancer properties in various cancers, the effects and mechanisms of eicosapentaenoic acid (EPA) in ovarian cancer cell growth are poorly understood.Materials and MethodsES2 ovarian clear cell carcinoma cells and SKOV3 adenocarcinoma cells were treated with palmitic acid or EPA, followed by flow cytometry and cell counting to measure apoptosis and proliferation, respectively. A modified protein lipid overlay assay was used to further verify whether EPA was a ligand of G protein–coupled receptor 30 (GPR30) in ES2 cells. The levels of apoptosis-related genes, phosphorylated AKT, and phosphorylated ERK1/2 were detected to explore the underlying mechanism. Finally, inhibitory effect of EPA on tumor growth via GPR30 was determined in vitro and in vivo.ResultsEPA suppressed ES2 ovarian clear cell carcinoma cells growth via GPR30, a novel EPA receptor, by inducing apoptosis. As a ligand of GPR30, EPA activated the GPR30-cAMP– protein kinase A signaling pathway. When GPR30 was suppressed by siRNA or its inhibitor G15, the antiproliferative action of EPA was impaired. Furthermore, EPA inhibited tumor growth by blocking the activation of AKT and ERK. In the mouse xenograft model, EPA decreased tumor volume and weight through GPR30 by blocking tumor cell proliferation.ConclusionThese results confirm that EPA is a tumor suppressor in human ovarian clear cell carcinoma cells and functions through a novel fatty acid receptor, GPR30, indicating a mechanistic linkage between omega-3 fatty acids and cancers. |
| Databáze: | OpenAIRE |
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