2. Academic Validation
  3. Eicosapentaenoic Acid Suppresses Tumor Growth and Enhances Chemosensitivity via AKT/mTOR Signaling in Uterine Serous Carcinoma

Eicosapentaenoic Acid Suppresses Tumor Growth and Enhances Chemosensitivity via AKT/mTOR Signaling in Uterine Serous Carcinoma

  • Cancers (Basel). 2026 Mar 31;18(7):1120. doi: 10.3390/cancers18071120.
Haomeng Zhang 1 2,  Weimin Kong 1,  Xiaochang Shen 1 2,  Shuning Chen 1 2,  Glenn Boyles 2,  Chelsey Vranes 2,  Miller Singleton 2,  Alexandra Diggs 2,  Chunxiao Zhou 2 3,  Victoria L Bae-Jump 2 3
Affiliations

Affiliations

  • 1 Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China.
  • 2 Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
PMID: 41976343 DOI: 10.3390/cancers18071120
Abstract

Background/objectives: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial Cancer characterized by high recurrence rates and poor response to conventional therapies, resulting in unfavorable clinical outcomes. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, has demonstrated anti-cancer activity in multiple malignancies.

Methods: This study used two USC cell lines, ARK1 and SPEC2, to evaluate the effects of EPA on cell proliferation, invasion, cell cycle profile, stress response, and Apoptosis. The potential synergistic effects of EPA combined with carboplatin were also examined. Western blotting was used to examine EPA's effects on downstream pathways related to cellular stress, inflammation, and epithelial-mesenchymal transition (EMT).

Results: EPA treatment markedly reduced cell proliferation and colony formation, with IC50 values of 28.96 µM for ARK-1 cells and 14.96 µM for SPEC-2 cells compared with control groups. It also induced G1 phase cell cycle arrest, increased cellular stress, triggered caspase-dependent apoptotic cell death, and suppressed invasive capacity. Moreover, EPA effectively counteracted TNF-α-stimulated upregulation of COX-2 and phosphorylated NF-κB. The combined treatment with EPA and carboplatin resulted in synergistic inhibition of cell viability and migration. Western blotting analysis showed that EPA attenuates the NF-κB and Akt/mTOR signaling pathways, promotes the expression of cellular stress-related proteins, and inhibits the expression of EMT-related proteins in both cell lines.

Conclusions: EPA exhibits potent anti-tumor activity against USC cells and enhances the efficacy of carboplatin. These data indicate that EPA has potential as a low-toxicity, multi-target Adjuvant treatment for USC, necessitating additional pre-clinical and clinical investigation.

Keywords

apoptosis; eicosapentaenoic acid (EPA); invasion; synergy; uterine serous carcinoma.

Figures
Products