Related Experiment Video
Updated: Jun 4, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Metformin-induced RBMS3 expression enhances ferroptosis and suppresses ovarian cancer progression
Yue Zhao1, Yixiao Wang1, Xinyi Zhang1
1Department of Oncology and Gynecology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui Province, China.
Abstract:
Metformin (Met), a widely used type II diabetes medication, has shown anti-cancer properties in various cancers. RBMS3 is a tumor suppressor implicated in several cancers, including ovarian cancer. Ferroptosis, a novel form of programmed cell death, is gaining attention in cancer research. This study explores whether metformin induces ferroptosis and inhibits ovarian cancer progression through the RBMS3 pathway. We used a CCK-8 assay to determine the optimal metformin concentration for ovarian cancer cells. Metformin's effects were further evaluated using EdU assay and flow cytometry. To clarify its mechanism, we employed programmed cell death inhibitors and measured levels of MDA (Malondialdehyde), GSH (Glutathione), and Fe²⁺. Ferroptosis-related proteins and RBMS3 expression in ovarian cancer tissues and cells were assessed via RT-qPCR and Western blotting. A xenograft mouse model was used to observe metformin's effects on tumor growth. Metformin inhibited the viability of ovarian cancer A2780 cells, promoted ferroptosis, increased MDA and Fe²⁺ levels, and reduced GSH. It upregulated ferroptosis-related genes while downregulating GPX4 and SLC7A11. Although RBMS3 was reduced in cancer cells, metformin increased its expression, and silencing RBMS3 reversed metformin's effects. In vivo, metformin inhibited tumor growth, which was negated by RBMS3 silencing. Our findings suggest that metformin promotes ferroptosis and inhibits ovarian cancer progression by upregulating RBMS3, offering a promising direction for clinical application in ovarian cancer treatment.
Insights
Metformin, a diabetes drug, combats ovarian cancer by inducing ferroptosis, a cell death process. It achieves this by increasing RBMS3 expression, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Metformin exhibits anti-cancer properties in various malignancies.
- RBMS3 acts as a tumor suppressor in cancers, including ovarian cancer.
- Ferroptosis, a distinct form of programmed cell death, is an emerging area in cancer research.
Purpose of the Study:
- To investigate if metformin induces ferroptosis in ovarian cancer cells.
- To determine if metformin inhibits ovarian cancer progression via the RBMS3 pathway.
- To explore the potential of metformin as an ovarian cancer therapeutic.
Main Methods:
- Cell viability assays (CCK-8, EdU), flow cytometry, and programmed cell death inhibitors were used.
- Levels of malondialdehyde (MDA), glutathione (GSH), and Fe²⁺ were quantified.
- Gene and protein expression of ferroptosis markers and RBMS3 were analyzed using RT-qPCR and Western blotting.
- In vivo efficacy was assessed using a xenograft mouse model.
Main Results:
- Metformin reduced ovarian cancer cell viability and promoted ferroptosis, indicated by increased MDA and Fe²⁺, and decreased GSH.
- Metformin modulated ferroptosis-related genes, downregulating GPX4 and SLC7A11.
- Metformin upregulated RBMS3 expression, which was diminished in cancer cells; RBMS3 knockdown abrogated metformin's anti-cancer effects.
- Metformin inhibited tumor growth in vivo, an effect reversed by RBMS3 silencing.
Conclusions:
- Metformin induces ferroptosis and suppresses ovarian cancer progression by upregulating RBMS3.
- The metformin-RBMS3 pathway presents a promising therapeutic target for ovarian cancer.
- Further clinical investigation of metformin for ovarian cancer treatment is warranted.
