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Updated: Dec 21, 2025

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
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A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

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Multi-Omics Analyses Reveal Mitochondrial Dysfunction Contributing to Temozolomide Resistance in Glioblastoma Cells

Huaijin Zhang1, Yuling Chen1, Xiaohui Liu1

  • 1MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Biomolecules
|September 28, 2023
PubMed

Insights

Glioblastoma (GBM) treatment resistance can be overcome. Mitochondrial dysfunction and elevated Ca2+ levels contribute to resistance, suggesting combined therapies targeting JNK or STAT3 pathways may improve glioblastoma outcomes.

Area of Science:

  • Neuro-oncology
  • Cancer Biology
  • Mitochondrial Medicine

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis.
  • Temozolomide (TMZ) is the standard chemotherapy, but resistance limits its effectiveness.

Purpose of the Study:

  • To investigate novel mechanisms of TMZ resistance in GBM.
  • To identify potential therapeutic strategies to overcome TMZ resistance.

Main Methods:

  • Generation of a TMZ-resistant GBM cell line.
  • Multi-omics and energy metabolism analyses.
  • Investigation of the role of mitochondrial dysfunction, calcium levels, and JNK-STAT3 pathway.

Main Results:

  • Mitochondrial dysfunction identified as a novel contributor to TMZ resistance.
  • Rotenone treatment partially induced TMZ resistance.
  • Elevated Ca2+ levels and activated JNK-STAT3 pathway were linked to TMZ resistance.
  • Inhibiting JNK or STAT3 enhanced GBM cell susceptibility to TMZ.

Conclusions:

  • Mitochondrial dysfunction, elevated Ca2+, and JNK-STAT3 pathway activation are key factors in GBM TMZ resistance.
  • Co-administering TMZ with JNK or STAT3 inhibitors shows promise for overcoming treatment resistance in glioblastoma.
Keywords:
chemoresistanceglioblastomamitochondrial dysfunctionmitochondrial retrograde signalingtemozolomide

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