Eicosapentaenoic acid exhibits antitumor effects and synergistically enhances carboplatin sensitivity in endometrial cancer
- 1Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health care Hospital
- 2Division of Gynecologic Oncology, University of North Carolina at Chapel Hill
- 3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Abstract
Background: Obesity-related metabolic dysfunction and chronic inflammation are well-established drivers of the carcinogenesis and progression of endometrial cancer (EC). Eicosapentaenoic acid (EPA) is a long-chain omega-3 polyunsaturated fatty acid that has previously demonstrated broad anti-inflammatory and anti-tumor properties in various cancer models. In this study, we evaluated the anti-tumorigenic effects of EPA in EC cell lines and in a genetically engineered mouse model of endometrioid EC.
Methods: Human EC cell lines, KLE and HEC-1B, were used to evaluate the effects of EPA alone or in combination with carboplatin on cell proliferation, invasion, cell cycle profile, stress response, and apoptosis. An LKB1 fl/fl p53 fl/fl genetically engineered mouse model of endometrioid EC was used to examine the effects of EPA on endometrial tumor growth.
Results: EPA treatment markedly suppressed cell proliferation and colony formation in a dose-dependent manner. Mechanistically, EPA induced G1 cell cycle arrest, promoted cellular stress, and activated cleaved caspases, while inhibiting cell adhesion and migration. These phenotypes were accompanied by robust inhibition of the AKT/mTOR signaling axis and activation of MAPK-mediated stress pathways. Inflammatory signaling was similarly attenuated, as evidenced by reduced TNF-α–induced COX-2 expression and decreased phosphorylation of NF-κB. Importantly, EPA synergized with carboplatin to enhance anti-tumor efficacy. Combination treatment produced stronger suppression of cell proliferation and invasion, increased apoptotic activity, and downregulation of key survival and oncogenic regulators, including phosphorylated AKT, Bcl-2, β-catenin, and CDK4. Four weeks of EPA administration significantly reduced endometrial tumor burden in both obese and lean mice, accompanied by decreased expression of Ki-67, Bcl-xL, β-catenin, and COX-2 in endometrial tumor tissues.
Conclusion: EPA exerts potent anti-tumor activity in EC through coordinated modulation of oncogenic signaling, inflammatory pathways, cellular stress responses, and apoptosis. Moreover, its ability to enhance carboplatin sensitivity highlights the potential of EPA as an adjuvant therapeutic candidate for EC and warrants further investigation in preclinical models of EC.
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BibTeX
@article{zhang2026eicosapentaenoic,
title = {{Eicosapentaenoic acid exhibits antitumor effects and synergistically enhances carboplatin sensitivity in endometrial cancer}},
author = {Haomeng Zhang and Weimin Kong and Shuning Chen and Xiaochang Shen and Alexandra Diggs and Miller Singleton and Boer Deng and Chelsey Vranes and Glenn Boyles and Chunxiao Zhou and Victoria Bae-Jump},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1960634},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1960634/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Eicosapentaenoic acid exhibits antitumor effects and synergistically enhances carboplatin sensitivity in endometrial cancer
AU - Haomeng Zhang
AU - Weimin Kong
AU - Shuning Chen
AU - Xiaochang Shen
AU - Alexandra Diggs
AU - Miller Singleton
AU - Boer Deng
AU - Chelsey Vranes
AU - Glenn Boyles
AU - Chunxiao Zhou
AU - Victoria Bae-Jump
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1960634
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1960634/full
AB - Background: Obesity-related metabolic dysfunction and chronic inflammation are well-established drivers of the carcinogenesis and progression of endometrial cancer (EC). Eicosapentaenoic acid (EPA) is a long-chain omega-3 polyunsaturated fatty acid that has previously demonstrated broad anti-inflammatory and anti-tumor properties in various cancer models. In this study, we evaluated the anti-tumorigenic effects of EPA in EC cell lines and in a genetically engineered mouse model of endometrioid EC. Methods: Human EC cell lines, KLE and HEC-1B, were used to evaluate the effects of EPA alone or in combination with carboplatin on cell proliferation, invasion, cell cycle profile, stress response, and apoptosis. An LKB1 fl/fl p53 fl/fl genetically engineered mouse model of endometrioid EC was used to examine the effects of EPA on endometrial tumor growth. Results: EPA treatment markedly suppressed cell proliferation and colony formation in a dose-dependent manner. Mechanistically, EPA induced G1 cell cycle arrest, promoted cellular stress, and activated cleaved caspases, while inhibiting cell adhesion and migration. These phenotypes were accompanied by robust inhibition of the AKT/mTOR signaling axis and activation of MAPK-mediated stress pathways. Inflammatory signaling was similarly attenuated, as evidenced by reduced TNF-α–induced COX-2 expression and decreased phosphorylation of NF-κB. Importantly, EPA synergized with carboplatin to enhance anti-tumor efficacy. Combination treatment produced stronger suppression of cell proliferation and invasion, increased apoptotic activity, and downregulation of key survival and oncogenic regulators, including phosphorylated AKT, Bcl-2, β-catenin, and CDK4. Four weeks of EPA administration significantly reduced endometrial tumor burden in both obese and lean mice, accompanied by decreased expression of Ki-67, Bcl-xL, β-catenin, and COX-2 in endometrial tumor tissues. Conclusion: EPA exerts potent anti-tumor activity in EC through coordinated modulation of oncogenic signaling, inflammatory pathways, cellular stress responses, and apoptosis. Moreover, its ability to enhance carboplatin sensitivity highlights the potential of EPA as an adjuvant therapeutic candidate for EC and warrants further investigation in preclinical models of EC.
SN - 1663-9812
ER -