Esomeprazole Alleviates Cisplatin Resistance by Inhibiting the AKT/mTOR Pathway in Ovarian Cancer Cells

Jingya Duan1, Zisen Zhang2, Jinfeng Du2

  • 1Department of Gynecology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.

PubMed
Abstract

Insights

Esomeprazole (ESO) shows anticancer effects on ovarian cancer cells, inhibiting growth and inducing apoptosis. It also enhances cisplatin

Area of Science:

  • Gynecologic Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Ovarian cancer is the leading cause of gynecologic cancer mortality.
  • Limited treatment options and platinum resistance necessitate novel therapeutic strategies.
  • Esomeprazole (ESO) exhibits preclinical and clinical anticancer activities.

Purpose of the Study:

  • To investigate the anticancer effects of esomeprazole (ESO) on ovarian cancer.
  • To elucidate the molecular mechanisms underlying ESO's action in ovarian cancer.
  • To evaluate ESO's potential in overcoming cisplatin resistance.

Main Methods:

  • Cell viability and proliferation assessed by CCK-8 and EdU assays.
  • Cell migration and invasion evaluated using Transwell assays.
  • Apoptosis detected by flow cytometry; protein expression analyzed via Western blotting and immunofluorescence.

Main Results:

  • ESO inhibited ovarian cancer cell viability, proliferation, migration, and invasion in a dose-dependent manner, while inducing apoptosis.
  • ESO modulated key proteins involved in cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT), including downregulation of c-MYC, SKP2, E2F1, N-cadherin, vimentin, MMP2, and PI3K/AKT/mTOR pathway, and upregulation of E-cadherin, caspase3, p53, BAX, and cleaved PARP.
  • Combination therapy with ESO and cisplatin demonstrated synergistic effects on cisplatin-resistant ovarian cancer cells, enhancing DNA damage (γH2A.X) and apoptosis.

Conclusions:

  • Esomeprazole exhibits significant anticancer activities against ovarian cancer.
  • ESO demonstrates synergistic efficacy with cisplatin, offering a promising strategy to improve chemosensitivity and overcome resistance in ovarian cancer.
  • The findings support ESO as a potential therapeutic agent for ovarian cancer, particularly in combination regimens.

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