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G Protein–Coupled Receptor 30 Mediates the Anticancer Effects Induced by Eicosapentaenoic Acid in Ovarian Cancer Cells
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Yue Zhao, Meng-Fei Zhao, Mei-Lin Yang, Tian-Yu Wu, Cong-Jian Xu, Jing-Mei Wang, Chao-Jun Li, Xi Li
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Cancer Res Treat. 2020;52(3):815-829. Published online March 5, 2020
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DOI: https://doi.org/10.4143/crt.2019.380
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 Abstract
 PDF Supplementary Material PubReader ePub
- Purpose
While 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 Methods
ES2 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.
Results
EPA 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.
Conclusion
These 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.
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Citations
Citations to this article as recorded by  - Integrative analysis of proteomics and lipidomic profiles reveal the fat deposition and meat quality in Duroc × Guangdong small spotted pig
Zhuosui Wu, Zhonggang Wang, Pan Wang, Leiyan Cheng, Jianhao Li, Yanfeng Luo, Linfang Yang, Linfeng Li, Jianhua Zeng, Bin Hu
Frontiers in Veterinary Science.2024;[Epub] CrossRef - The G Protein-Coupled Estrogen Receptor GPER in the Development and Progression of Cancer
Liliana Torres-López, Miguel Olivas-Aguirre, Oxana Dobrovinskaya
Receptors.2024; 3(2): 220. CrossRef - ACSL4-Mediated Membrane Phospholipid Remodeling Induces Integrin β1 Activation to Facilitate Triple-Negative Breast Cancer Metastasis
Yuxiang Qiu, Xing Wang, Yan Sun, Ting Jin, Rui Tang, Xinyue Zhou, Ming Xu, Yubi Gan, Rui Wang, Haojun Luo, Manran Liu, Xi Tang
Cancer Research.2024; 84(11): 1856. CrossRef - The Role of Estrogen across Multiple Disease Mechanisms
Xiuting Xiang, Praneetha Palasuberniam, Rahmawati Pare
Current Issues in Molecular Biology.2024; 46(8): 8170. CrossRef - Role of Estrogen Receptor β, G-Protein Coupled Estrogen Receptor and Estrogen-Related Receptors in Endometrial and Ovarian Cancer
Susanne Schüler-Toprak, Maciej Skrzypczak, Carsten Gründker, Olaf Ortmann, Oliver Treeck
Cancers.2023; 15(10): 2845. CrossRef - Divergent Metabolic Effects of Metformin Merge to Enhance Eicosapentaenoic Acid Metabolism and Inhibit Ovarian Cancer In Vivo
Mary P. Udumula, Laila M. Poisson, Indrani Dutta, Nivedita Tiwari, Seongho Kim, Jasdeep Chinna-Shankar, Ghassan Allo, Sharif Sakr, Miriana Hijaz, Adnan R. Munkarah, Shailendra Giri, Ramandeep Rattan
Cancers.2022; 14(6): 1504. CrossRef - Functional metabolomics revealed functional metabolic-characteristics of chronic hepatitis that is significantly differentiated from acute hepatitis in mice
Tianyu Wang, Longlong Hu, Jiongjiong Lu, Mengqing Xiao, Jinging Liu, Huiyu Xia, Haitao Lu
Pharmacological Research.2022; 180: 106248. CrossRef - Effects of Omega-3 Intake on Adolescent Health
Xiuyuan Zhang
Highlights in Science, Engineering and Technology.2022; 19: 89. CrossRef - Determination of lipid profiles of Dezhou donkey meat using an LC‐MS‐based lipidomics method
Mengmeng Li, Mingxia Zhu, Wenqiong Chai, Yonghui Wang, Dongmei Fan, Mengqing Lv, Xiaojing Jiang, Yongxiang Liu, Qingxin Wei, Changfa Wang
Journal of Food Science.2021; 86(10): 4511. CrossRef - Connexins and cAMP Cross-Talk in Cancer Progression and Metastasis
Chang-Xu Chen, Kai-Jun Luo, Jia-Peng Yang, Yun-Chao Huang, Eduardo R. Cardenas, Bruce J. Nicholson, Jean X. Jiang
Cancers.2020; 13(1): 58. CrossRef
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Prognostic Value of TP53 Mutation for Transcatheter Arterial Chemoembolization Failure/Refractoriness in HBV-Related Advanced Hepatocellular Carcinoma
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Miao Xue, Yanqin Wu, Wenzhe Fan, Jian Guo, Jialiang Wei, Hongyu Wang, Jizhou Tan, Yu Wang, Wang Yao, Yue Zhao, Jiaping Li
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Cancer Res Treat. 2020;52(3):925-937. Published online March 30, 2020
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DOI: https://doi.org/10.4143/crt.2019.533
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Abstract
PDFPubReaderePub
- Purpose
This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE).
Materials and Methods
From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA).
Results
Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness.
Conclusion
Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.
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Citations
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Baokun Liu, Lujun Shen, Wen Liu, Zhiyong Zhang, Jieqiong Lei, Zhengguo Li, Qinquan Tan, Hengfei Huang, Xingdong Wang, Weijun Fan
Journal of Hepatocellular Carcinoma.2024; Volume 11: 1557. CrossRef - Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE
Libo Wang, Jiahui Cao, Zaoqu Liu, Shitao Wu, Yin Liu, Ruopeng Liang, Rongtao Zhu, Weijie Wang, Jian Li, Yuling Sun
Hepatology Communications.2024;[Epub] CrossRef - Development and validation of survival prediction models for patients with hepatocellular carcinoma treated with transcatheter arterial chemoembolization plus tyrosine kinase inhibitors
Kun Huang, Haikuan Liu, Yanqin Wu, Wenzhe Fan, Yue Zhao, Miao Xue, Yiyang Tang, Shi-Ting Feng, Jiaping Li
La radiologia medica.2024; 129(11): 1597. CrossRef - Identification of BRD7 by whole-exome sequencing as a predictor for intermediate-stage hepatocellular carcinoma in patients undergoing TACE
Kun Huang, Yanqin Wu, Wenzhe Fan, Yue Zhao, Miao Xue, Haikuan Liu, Yiyang Tang, Jiaping Li
Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11247. CrossRef - Prediction model of no-response before the first transarterial chemoembolization for hepatocellular carcinoma: TACF score
Jia-Wei Zhong, Dan-Dan Nie, Ji-Lan Huang, Rong-Guang Luo, Qing-He Cheng, Qiao-Ting Du, Gui-Hai Guo, Liang-Liang Bai, Xue-Yun Guo, Yan Chen, Si-Hai Chen
Discover Oncology.2023;[Epub] CrossRef - Mechanisms of Pharmacoresistance in Hepatocellular Carcinoma: New Drugs but Old Problems
Jose J.G. Marin, Marta R. Romero, Elisa Herraez, Maitane Asensio, Sara Ortiz-Rivero, Anabel Sanchez-Martin, Luca Fabris, Oscar Briz
Seminars in Liver Disease.2022; 42(01): 087. CrossRef - Non-Apoptotic Programmed Cell Death-Related Gene Signature Correlates With Stemness and Immune Status and Predicts the Responsiveness of Transarterial Chemoembolization in Hepatocellular Carcinoma
Guixiong Zhang, Wenzhe Fan, Hongyu Wang, Jie Wen, Jizhou Tan, Miao Xue, Jiaping Li
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef - Plasma arginase-1 as a predictive marker for early transarterial chemoembolization refractoriness in unresectable hepatocellular carcinoma
Wei-Li Xia, Shi-Jun Xu, Yuan Guo, Xiao-Hui Zhao, Hong-Tao Hu, Yan Zhao, Quan-Jun Yao, Lin Zheng, Dong-Yang Zhang, Chen-Yang Guo, Wei-Jun Fan, Hai-Liang Li
Frontiers in Oncology.2022;[Epub] CrossRef - Useful genes for predicting the efficacy of transarterial chemoembolization in hepatocellular carcinoma
Yuan Guo, Hongtao Hu, Shijun Xu, Weili Xia, Hailiang Li
Journal of Cancer Research and Therapeutics.2022; 18(7): 1860. CrossRef - Development and Validation of a Predictive Model for Early Refractoriness of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma
Tian-Cheng Wang, Tian-Zhi An, Jun-Xiang Li, Zi-Shu Zhang, Yu-Dong Xiao
Frontiers in Molecular Biosciences.2021;[Epub] CrossRef - Transcatheter arterial chemoembolization followed by surgical resection for hepatocellular carcinoma: a focus on its controversies and screening of patients most likely to benefit
Zhan-Qi Wei, Yue-Wei Zhang
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Young Chang, Soung Won Jeong, Jae Young Jang, Yong Jae Kim
International Journal of Molecular Sciences.2020; 21(21): 8165. CrossRef
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