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Updated: Dec 20, 2025

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Knockdown of Amphiregulin Triggers Doxorubicin-Induced Autophagic and Apoptotic Death by Regulating Endoplasmic

I-Neng Lee1, Jen-Tsung Yang2,3, Ming-Ju Hsieh4,5,6,7

  • 1Department of Medical Research, Chang Gung Memorial Hospital, Chiayi, 61363, Taiwan.

Journal of Molecular Neuroscience : MN
|May 31, 2020
PubMed

Insights

Targeting amphiregulin (AREG) enhances doxorubicin (Dox) treatment efficacy in glioblastoma multiforme (GBM) by increasing cell death. AREG is a potential therapeutic target and biomarker for improved GBM survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis and limited treatment options.
  • Doxorubicin (Dox) shows potential for GBM treatment, but efficacy is hindered by factors like drug resistance.
  • Amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, is implicated in cancer progression and drug resistance.

Purpose of the Study:

  • To investigate the role of AREG in Dox treatment of GBM.
  • To elucidate the molecular mechanisms by which AREG influences Dox efficacy.
  • To evaluate AREG as a potential therapeutic target and biomarker in GBM.

Main Methods:

  • Knockdown of AREG in GBM cells.
  • Assessment of Dox-induced endoplasmic reticulum (ER) stress, autophagy, and apoptosis.
  • Bioinformatic analysis of AREG expression in GBM tissues.
  • Antibody array analysis to identify AREG-activated pathways.

Main Results:

  • Knockdown of AREG potentiated Dox-induced ER stress, autophagy, and apoptosis in GBM cells, leading to cell death.
  • High AREG expression in GBM tissues correlated with poor patient survival.
  • AREG is involved in pathways activated in GBM, suggesting its oncogenic role.

Conclusions:

  • AREG plays a significant role in Dox treatment resistance in GBM.
  • Reducing AREG levels can enhance the effectiveness of Dox therapy.
  • AREG represents a promising therapeutic target and predictive biomarker for GBM treatment.
Keywords:
AmphiregulinAutophagyDoxorubicinDrug resistanceEndoplasmic reticulum (ER) stressGlioblastoma multiforme (GBM)

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