Molecular radiobiology3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226
Section snippets
Cell culture
UT-SCC15, UT-SCC45 (Ref. in [41]) and FaDu human head and neck squamous cell carcinoma (HNSCC) cell lines as well as A549 human lung cancer, DLD-1 and HCT-116 human colorectal carcinoma, MiaPaCa2 and Panc1 human pancreatic carcinoma cell lines were obtained from ATCC (Rockville, USA). Cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM; PAA, Cölbe, Germany) containing glutamax-I (l-alanyl-l-glutamine) supplemented with 10% fetal calf serum (FCS; PAA) and 1% non-essential amino acids
TAE226 reduces clonogenic survival dose- and time-dependently
Clonogenic survival was determined in 3D tumor cell cultures upon treatment with the FAK inhibitor TAE226 (Fig. 1a and b). Increasing concentrations of TAE226 significantly (p < 0.05) diminished clonogenic survival of 3D grown FaDu, UT-SCC15, UT-SCC45 (all HNSCC), A549 (lung cancer), DLD-1, HCT-116 (colorectal carcinoma) and MiaPaCa2 (pancreatic carcinoma) cells after a 1-h treatment in comparison to DMSO control (Fig. 1c). A 24-h treatment resulted in further reduction of clonogenicity in all
Discussion
The development and progression of SCC is thought to be critically dependent on integrins and their downstream signal transduction [46]. As FAK is well known to channel prosurvival cues from both integrins and growth factor receptors, we assessed, for the first time, the effects of pharmacological FAK inhibition using TAE226 in HNSCC in combination with irradiation, which is part of the standard therapy of this disease. The major findings generated in a more physiological 3D cell culture model
Acknowledgements
The research and the authors were in part supported by a Grant from the Bundesministerium für Bildung und Forschung (BMBF Contract 03ZIK041). The pharmacological FAK inhibitor TAE226 was kindly provided by Novartis (Switzerland).
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