Mifepristone achieves tumor suppression and ferroptosis through PR/p53/HO1/GPX4 axis in meningioma cells.

Abstract

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.