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Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response

Martynas Drigotas1, Annette Affolter, Wolf J Mann

  • 1Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
|March 14, 2013
PubMed
Abstract

Insights

Irradiation-induced reactive oxygen species (ROS) activate the MAPK pathway and vascular endothelial growth factor (VEGF) release in head and neck cancer. This mechanism may impact radiotherapy effectiveness and tumor cell response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Radiotherapy resistance is a significant challenge in head and neck squamous cell carcinoma (HNSCC) treatment.
  • Previous research indicated post-radiotherapy mitogen-activated protein kinase (MAPK) pathway activation and vascular endothelial growth factor (VEGF) release contribute to reduced tumor cell response.
  • This study investigates the role of reactive oxygen species (ROS) in this mechanism under irradiation (IR).

Purpose of the Study:

  • To examine the association between irradiation-induced ROS and the activation of the MAPK pathway and VEGF release in HNSCC.
  • To understand the contribution of ROS to radioresistance in head and neck cancer.

Main Methods:

  • Measurement of intracellular ROS levels following IR.
  • Modeling of radiation-induced ROS using hydrogen peroxide (H2O2) exposure in HNSCC cell lines.
  • Assessment of ERK phosphorylation and VEGF levels using Western blot, immunohistochemistry, and ELISA.

Main Results:

  • Elevated phosphorylated ERK (pERK) levels were observed after IR and H2O2 treatment, which were suppressed by U0126.
  • Increased intracellular VEGF levels were detected following H2O2 application.
  • Irradiation-induced ROS were found to activate the MAPK pathway and stimulate VEGF release.

Conclusions:

  • Irradiation-induced ROS play a crucial role in activating the MAPK pathway and releasing VEGF in HNSCC.
  • VEGF release, known to confer cytoprotection after cellular distress, may contribute to radioresistance.
  • Understanding this ROS-MAPK-VEGF axis is potentially important for improving radiotherapy outcomes in head and neck cancer.
Keywords:
MAP kinase pathwayhead and neck squamous cell carcinomairradiationreactive oxygen speciesvascular endothelial growth factor

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