Effect of Mitochondrial Fission Inhibition on Apoptosis in Glioblastoma Multiforme (GBM) Cells

Abstract

Aim: Glioblastoma multiforme (GBM) is characterized by poor prognosis and therapeutic resistance. Mitochondrial dynamics, particularly mitochondrial fission regulated by DRP1, play a critical role in apoptosis. This study aimed to investigate the effect of mitochondrial fission inhibition on apoptosis in U87 wild-type cells and to evaluate the potential synergistic therapeutic effect of combining mitochondrial fission inhibition with temozolomide (TMZ).Materials and methods: The cytotoxic effects and IC₅₀ values of Mdivi-1 and TMZ were determined by a 72-hour MTT assay. Based on these results, 50 μM Mdivi-1 was selected for combination treatment with 50 μM TMZ, and the expression levels of DRP1, FIS1, BAX, and BCL2 were analyzed by qRT-PCR.Results: Mitochondrial fission inhibition significantly reduced cell viability (p < 0.05). Combination treatment with Mdivi-1 and TMZ further decreased cell viability compared with the control group. qRT-PCR analysis revealed a significant decrease in BCL2 mRNA expression following Mdivi-1 treatment,whereas changes in DRP1, FIS1, and BAX expression were not statistically significant.Conclusion: These findings suggest that inhibition of mitochondrial fission may enhance the antiproliferative effect of TMZ in GBM cells. Targeting mitochondrial dynamics may represent a potential therapeutic strategy for overcoming treatment resistance; however, further studies are required to clarify the underlying molecular mechanisms.