Document Detail


Dose-dependent and sequence-dependent cytotoxicity of erlotinib and docetaxel in head and neck squamous cell carcinoma.
MedLine Citation:
PMID:  18418213     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to determine whether the efficacy of taxoid treatment combined with epidermal growth factor receptor (EGFR) inhibition is dose and sequence dependent in head and neck squamous cell carcinoma. Three head and neck squamous cell carcinoma cell lines, chosen on the basis of their diverse EGFR expression levels, were treated with docetaxel, erlotinib, or both. The combination index was calculated using the Chou-Talalay equation. Propidium iodide staining with fluorescence-activated cell sorting analysis was used to evaluate the effects of drugs on cell cycle changes. Western blot analysis was used to determine the effects of agents on cell signaling pathways. Administration of low-dose docetaxel (0.1-3 nmol/l) concurrently or before erlotinib had additive cytotoxic effects in two cell lines but was antagonistic in one line, whereas low-dose docetaxel after erlotinib was synergistic in all cell lines. In contrast, high-dose docetaxel (40 nmol/l) resulted in more apoptosis when given before, rather than after or concurrently with, erlotinib. Low-dose docetaxel induced an accumulation of cells in the sub-G0 phase of the cell cycle with no mitotic arrest or apoptosis, whereas high-dose docetaxel induced mitotic arrest and apoptosis. The low and high doses of docetaxel had opposite effects on EGFR expression: a decrease and an increase, respectively. The dose of docetaxel affects sequence-dependent cytotoxicity when docetaxel is combined with an EGFR inhibitor. The mechanism for this difference is a combination of the dose-dependent effects of docetaxel on the mode of cell death and on EGFR expression.
Authors:
Babita Saigal; Bonnie S Glisson; Faye M Johnson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  19     ISSN:  0959-4973     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-04-17     Completed Date:  2008-09-15     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  465-75     Citation Subset:  IM    
Affiliation:
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / administration & dosage,  pharmacology*
Apoptosis / drug effects
Blotting, Western
Carcinoma, Squamous Cell
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Antagonism
Drug Synergism
Head and Neck Neoplasms
Humans
Quinazolines / administration & dosage,  pharmacology*
Receptor, Epidermal Growth Factor / antagonists & inhibitors
Taxoids / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Quinazolines; 0/Taxoids; 15H5577CQD/docetaxel; EC 2.7.10.1/Receptor, Epidermal Growth Factor; J4T82NDH7E/erlotinib

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