| 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. | |
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MedLine Citation:
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PMID: 22348829 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Haiquan Lu; Ke Liang; Yang Lu; Zhen Fan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-02-17 |
Journal Detail:
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Title: Cancer letters Volume: 322 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-05-28 Completed Date: 2012-08-03 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 78-85 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Houston, 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies, Monoclonal
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pharmacology* Antineoplastic Agents / pharmacology* Carcinoma, Squamous Cell / radiotherapy* Cell Line, Tumor Genes, ras Head and Neck Neoplasms / radiotherapy* Humans 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* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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CA016672/CA/NCI NIH HHS; R01 CA129036/CA/NCI NIH HHS; R01 CA129036-04/CA/NCI NIH HHS; R21 DE021883/DE/NIDCR NIH HHS; R21 DE021883-01/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/RNA, Small Interfering; 0/Radiation-Sensitizing Agents; 0/cetuximab; EC 2.7.10.1/Receptor, Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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