The anti-EGFR antibody cetuximab sensitizes human head and neck squamous cell carcinoma cells to radiation in part through inhibiting radiation-induced upregulation of HIF-1α

Haiquan Lu, Ke Liang, Yang Lu, Zhen Fan

Research output: Contribution to journalArticle

Abstract

In this study, we investigated the mechanisms underlying cetuximab-mediated radiosensitization of HNSCC. Irradiation of HNSCC cells upregulated hypoxia-inducible factor-1 alpha (HIF-1α) via a mechanism involving de novo synthesis of HIF-1α protein. Radiation-induced upregulation of HIF-1α was completely abolished by concurrent treatment of HNSCC cells with cetuximab. Experimental elevation of constitutively expressed HIF-1α abolished cetuximab-mediated radiosensitization in HNSCC cells, whereas downregulation of HIF-1α by siRNA or a small molecule inhibitor enhanced responses of cetuximab-resistant HNSCC cells to cetuximab plus radiation. Our data suggest that cetuximab sensitizes cancer cells to ionizing radiation in part through inhibition of radiation-induced upregulation of HIF-1α.

Original languageEnglish (US)
Pages (from-to)78-85
Number of pages8
JournalCancer Letters
Volume322
Issue number1
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Keywords

  • Cetuximab
  • EGFR
  • HIF-1alpha
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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