ArticleJournal of ovarian research2024
Synergistic suppression of ovarian cancer by combining NRF2 and GPX4 inhibitors: in vitro and in vivo evidence.
Article in Journal of ovarian research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Recent advancements in NRF2-regulated ferroptosis modulation for targeted cancer therapy.Molecular biology reports · 2026Review
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- The Role of Se-Containing Glutathione Peroxidases and Thioredoxin Reductases in Oncogenesis: Expression Paradoxes and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Advances in ferroptosis research in ovarian cancer: molecular mechanisms and therapeutic perspectives.American journal of cancer research · 2026Review
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- Impact of oxidative stress on malignant tumor progression and emerging therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- Ferroptosis and cancer: when iron turns against tumors.Cellular and molecular life sciences : CMLS · 2025Review
- Long non-coding RNA HCP5 accelerated malignant progression of ovarian cancer by inhibiting ferroptosis through interaction with polypyrimidine tract binding protein 1.Journal of ovarian research · 2025Article
- Ferroptosis in Cancer: Mechanism and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Ovarian cancer is a significant challenge in women's health due to the lack of effective screening and diagnostic methods, often leading to late detection and the highest mortality rate among all gynecologic tumors worldwide. Recent research has shown that ovarian cancer has an "iron addiction" phenotype which makes it vulnerable to ferroptosis inducers. We tested the combination of NRF2-targeted inhibitors with GPX4-targeted inhibitors in ovarian cancer through in vitro and in vivo experiment. The data showed that combination treatment effectively suppressed adherent cell growth, inhibited suspended cell spheroid formation, and restrained the ability of spheroid formation in 3D-culture. Mechanistically, the combination induced accumulation of ROS, 4-HNE, as well as activation of caspase-3 which indicates that this combination simultaneously increases cell ferroptosis and apoptosis. Notably, inhibition of GPX4 or NRF2 can suppress ovarian cancer spreading and growth in the peritoneal cavity of mice, while the combination of NRF2 inhibitor ML385 with GPX4 inhibitors showed a significant synergistic effect compared to individual drug treatment in a syngeneic mouse ovarian cancer model. Overall, these findings suggest that combining NRF2 inhibitors with GPX4 inhibitors results in a synergy suppression of ovarian cancer in vitro and in vivo, and maybe a promising therapeutic strategy for the treatment of ovarian cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.