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Updated: Jul 4, 2026

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

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

Published on: March 28, 2021

Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular

Na Ning1, Changtu Wang2, Tingyu Gao3

  • 1Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.

Molecular Carcinogenesis
|July 2, 2026
PubMed

Insights

Acylglycerol kinase (AGK) influences glioblastoma (GBM) progression and temozolomide (TMZ) resistance by modulating cellular senescence (CSEN). Targeting AGK and CSEN enhances TMZ therapy efficacy in GBM patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Temozolomide (TMZ) is the standard first-line treatment for glioblastoma (GBM), but drug resistance remains a significant clinical challenge.
  • Cellular senescence (CSEN) plays a complex role in tumor progression and is linked to mitochondrial dysfunction.
  • Acylglycerol kinase (AGK), a mitochondrial kinase, is implicated in mitochondrial function and reactive oxygen species (ROS) production.

Purpose of the Study:

  • To investigate the role of AGK in GBM progression and TMZ resistance.
  • To determine if CSEN mediates AGK's effects on TMZ resistance.
  • To explore the therapeutic potential of senolytic agents in combination with TMZ.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) data for AGK expression and patient prognosis.
  • In vitro cell experiments involving AGK knockdown and overexpression.
  • Assessment of mitochondrial ROS (mtROS), mitochondrial membrane potential, and apoptosis.
  • Treatment with Mito-TEMPO (mtROS scavenger) and FOXO4-DRI (senolytic agent).

Main Results:

  • Increased AGK expression correlates with poor GBM patient prognosis.
  • AGK suppression inhibits GBM cell proliferation but paradoxically enhances TMZ resistance by amplifying CSEN via increased mtROS and decreased mitochondrial membrane potential.
  • Mito-TEMPO and FOXO4-DRI reversed TMZ resistance by promoting apoptosis of senescent cells, thereby enhancing TMZ efficacy.
  • Clinical analysis confirmed the link between AGK levels, CSEN, and TMZ treatment outcomes in GBM patients.

Conclusions:

  • Senescence induction is a novel mechanism underlying AGK-mediated TMZ sensitization in GBM.
  • Co-targeting AGK and CSEN presents a promising therapeutic strategy to overcome TMZ resistance in glioblastoma.
  • Modulating AGK and senescent cells offers a potential avenue for improving GBM treatment outcomes.
Keywords:
Temozolomideacylglycerol kinasecellular senescenceglioblastomamitochondrial ROS

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