Document Detail


3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226.
MedLine Citation:
PMID:  19729215     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Focal adhesion kinase (FAK), a main player in integrin signaling and survival, is frequently overexpressed in human cancers and therefore postulated as potential target in cancer therapy. The aim of this study was to evaluate the radiosensitizing potential of the FAK inhibitor TAE226 in three-dimensional (3D) tumor cell cultures. MATERIALS AND METHODS: Head and neck squamous cell carcinoma (HNSCC) cells (FaDu, UT-SCC15, UT-SCC45), lung cancer cells (A549), colorectal carcinoma cells (DLD-1, HCT-116) and pancreatic tumor cells (MiaPaCa2, Panc1) were treated with different concentrations of TAE226 (0-1mum; 1 or 24h) without or in combination with irradiation (0-6Gy, X-ray, single dose). Subsequently, 3D clonogenic survival assays (laminin-rich extracellular matrix) and Western blotting (expression/phosphorylation, e.g. FAK, Akt, ERK1/2) were performed. RESULTS: All investigated 3D cell cultures showed a dose-dependent reduction in clonogenic survival by TAE226. Intriguingly, TAE226 only significantly radiosensitized 3D HNSCC cell cultures accompanied by a pronounced dephosphorylation of FAK, Akt and ERK1/2. CONCLUSIONS: Our data demonstrate TAE226 as potent FAK inhibitor that enhances the cellular radiosensitivity particularly of HNSCC cells grown in a 3D cell culture model. Future in vitro and in vivo investigations will clarify, to which extent this approach might be clinically relevant for radiotherapy of HNSCC.
Authors:
Stephanie Hehlgans; Inga Lange; Iris Eke; Nils Cordes
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-02
Journal Detail:
Title:  Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology     Volume:  92     ISSN:  1879-0887     ISO Abbreviation:  Radiother Oncol     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-15     Completed Date:  2010-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8407192     Medline TA:  Radiother Oncol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  371-8     Citation Subset:  IM    
Affiliation:
OncoRay-Center for Radiation Research in Oncology, Dresden University of Technology, Dresden, Germany.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Carcinoma, Squamous Cell / pathology,  radiotherapy
Cell Movement / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects*,  radiation effects*
Colorectal Neoplasms / pathology,  radiotherapy
Dose-Response Relationship, Drug
Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*,  metabolism
Head and Neck Neoplasms / pathology,  radiotherapy
Humans
Lung Neoplasms / pathology,  radiotherapy
Morpholines / pharmacology*
Pancreatic Neoplasms / pathology,  radiotherapy
Probability
Radiation Tolerance / drug effects
Radiation, Ionizing
Tumor Cells, Cultured / drug effects
Chemical
Reg. No./Substance:
0/Morpholines; 0/TAE226; EC 2.7.10.2/Focal Adhesion Protein-Tyrosine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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