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Mifepristone achieves tumor suppression and ferroptosis through PR/p53/HO1/GPX4 axis in meningioma cells
Qin Dai1,2, Jinfei Wei1,2, Ziwei Li1,2
1National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
Purpose:
This study explores the effects of mifepristone on the proliferation, motility, and invasion of malignant and benign meningioma cells, aiming to identify mifepristone-sensitive types and investigate the underlying molecular mechanisms.
Methods:
IOMM-Lee and HBL-52 meningioma cells were treated with 0, vehicle control (VC), 5, 10, 20, 40, and 80 μM of mifepristone for 12, 24, 48, 72, and 96 h. Proliferation was assessed via CCK8 assay, while motility and invasion were measured using wound scratch and transwell assays. RNA sequencing and RT-PCR were used to analyze gene expression changes.
Results:
Mifepristone inhibited proliferation, motility, and invasion in both IOMM-Lee and HBL-52 cells in a dose- and time-dependent manner. RNA sequencing showed up-regulated genes significantly enriched in the ferroptosis pathway in both cell lines, confirmed by increased p53 and HO1 expression, decreased GPX4 expression, lipid peroxidation, Fe2+ accumulation, and ROS release. Immunofluorescence staining and RT-PCR also revealed a corresponding decrease in mifepristone-related progesterone receptor expression.
Conclusion:
Mifepristone induces ferroptosis in meningioma cells via the PR/p53/HO1/GPX4 axis, suggesting its potential as a treatment for ferroptosis-sensitive meningiomas. It also supplies new clues regarding ferroptosis as a treatment entry point for meningiomas.
Insights
Mifepristone effectively inhibits meningioma cell growth, motility, and invasion by inducing ferroptosis. This mechanism involves the progesterone receptor (PR) pathway, offering a potential new treatment strategy for meningiomas.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Meningiomas are tumors arising from the meninges.
- Understanding molecular mechanisms driving meningioma growth is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the effects of mifepristone on malignant and benign meningioma cell behavior.
- To elucidate the molecular pathways targeted by mifepristone in meningioma cells.
Main Methods:
- Meningioma cell lines (IOMM-Lee, HBL-52) were treated with varying concentrations of mifepristone.
- Cell proliferation, motility, and invasion were assessed using CCK8, wound scratch, and transwell assays.
- Gene expression analysis was performed using RNA sequencing and RT-PCR.
Main Results:
- Mifepristone demonstrated dose- and time-dependent inhibition of proliferation, motility, and invasion in both cell lines.
- RNA sequencing revealed significant enrichment of ferroptosis pathway genes, with increased p53 and HO1, and decreased GPX4 expression.
- Evidence of lipid peroxidation, Fe2+ accumulation, ROS release, and reduced progesterone receptor (PR) expression confirmed ferroptosis induction.
Conclusions:
- Mifepristone induces ferroptosis in meningioma cells through the PR/p53/HO1/GPX4 signaling axis.
- These findings suggest mifepristone as a potential therapeutic agent for ferroptosis-sensitive meningiomas.
- Ferroptosis represents a promising therapeutic entry point for meningioma treatment.
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