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

IF 3.2 2区 医学 Q2 CLINICAL NEUROLOGY Journal of Neuro-Oncology Pub Date : 2025-01-03 DOI:10.1007/s11060-024-04918-6
Qin Dai, Jinfei Wei, Ziwei Li, Ting Li, Yenan Fang, Xinyu Li, Bingyan Shen, Qiqi Xie, Min Wang, Wencan Wu
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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.

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索莱宝 Malondialdehyde(MDA) Content Assay Kit
BC0025
索莱宝 Reduced Glutathione(GSH) Content Assay Kit
BC1175
索莱宝 crystal violet
C8470
来源期刊
Journal of Neuro-Oncology
Journal of Neuro-Oncology 医学-临床神经学
CiteScore
6.60
自引率
7.70%
发文量
277
审稿时长
3.3 months
期刊介绍: The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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