3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226

Radiother Oncol. 2009 Sep;92(3):371-8. doi: 10.1016/j.radonc.2009.08.001. Epub 2009 Sep 2.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects*
  • Cell Survival / radiation effects*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / radiotherapy
  • Dose-Response Relationship, Drug
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • Morpholines / pharmacology*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / radiotherapy
  • Probability
  • Radiation Tolerance / drug effects
  • Radiation, Ionizing
  • Tumor Cells, Cultured / drug effects


  • Morpholines
  • TAE226
  • Focal Adhesion Protein-Tyrosine Kinases