Targeting mitochondrial fission enhances radiosensitivity in glioblastoma
LIANG Lei
ZHANG Jianning
GUO Jingyu
SUN Junzhao
KELANG Muerzhahan
LV Wenying
Abstract：Objective To investigate the regulatory role of mitochondrial fission in glioblastoma multiforme(GBM)radiosensitivity and its underlying mechanisms.Methods U251 and U87 cells were treated with mitofusin inhibitor 8(MFI8)to induce mitochondrial fission combined with X-ray irradiation.Mitochondrial morphology was observed by laser confocal microscopy.Cell proliferation was assessed via colony formation assay,apoptosis by TUNEL staining,reactive oxygen species(ROS)levels using DCFH-DA probe,and heme oxygenase 1(HMOX1)protein/superoxide dismutase 1(SOD1)mRNA expression by Western blot and qPCR respectively.Results MFI8 significantly reduced mitochondrial aspect ratio by 19.4%(U251,P=0.009 9)and 35.5%(U87,P=0.001 3).Synergized with X-rays,MFI8 could inhibit proliferation,promote apoptosis,induce ROS accumulation and downregulate SOD1 transcription and HMOX1 expression(P<0.05).Conclusion Mitochondrial fission enhances GBM radiosensitivity through SOD1 transcriptional suppression,HMOX1 downregulation,and ROS overload-induced oxidative stress.Targeting mitochondrial dynamics may serve as a novel strategy to optimize radiotherapy efficacy.
Keywords：Mitochondrial fissionGlioblastomaRadiosensitivityX-RaysOxidative stress
Publication Date：2025-08-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 22-28 )