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 language | English (US) |
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Pages (from-to) | 78-85 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 322 |
Issue number | 1 |
DOIs | |
State | Published - Sep 1 2012 |
Externally published | Yes |
Keywords
- Cetuximab
- EGFR
- HIF-1alpha
- Radiation
ASJC Scopus subject areas
- Oncology
- Cancer Research