Document Detail

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.
MedLine Citation:
PMID:  22348829     Owner:  NLM     Status:  MEDLINE    
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.
Haiquan Lu; Ke Liang; Yang Lu; Zhen Fan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-17
Journal Detail:
Title:  Cancer letters     Volume:  322     ISSN:  1872-7980     ISO Abbreviation:  Cancer Lett.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-08-03     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  78-85     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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MeSH Terms
Antibodies, Monoclonal / pharmacology*
Antibodies, Monoclonal, Humanized
Antineoplastic Agents / pharmacology*
Carcinoma, Squamous Cell / radiotherapy*
Cell Line, Tumor
Genes, ras
Head and Neck Neoplasms / radiotherapy*
Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*,  genetics,  physiology
RNA, Small Interfering / genetics
Radiation Tolerance
Radiation-Sensitizing Agents / pharmacology*
Receptor, Epidermal Growth Factor / antagonists & inhibitors*
Grant Support
CA016672/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS; R01 CA129036/CA/NCI NIH HHS; R01 CA129036/CA/NCI NIH HHS; R01 CA129036-04/CA/NCI NIH HHS; R21 DE021883/DE/NIDCR NIH HHS; R21 DE021883/DE/NIDCR NIH HHS; R21 DE021883-01/DE/NIDCR NIH HHS
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antineoplastic Agents; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/RNA, Small Interfering; 0/Radiation-Sensitizing Agents; EC, Epidermal Growth Factor; PQX0D8J21J/cetuximab

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