Article
Tumour and fibroblast cell lines as an in vitro-tumour model system for HNSCC: Efficacy analysis of kinase inhibitors in combination with irradiation
Search Medline for
Authors
Published: | August 3, 2011 |
---|
Outline
Text
Introduction: The emergence of radioresistance has become one of the most significant issues in the treatment of head and neck squamous cell carcinomas. We have previously demonstrated that the radiation-induced activation of MAP kinase ERK and subsequently VEGF might cause decreased radiosensitivity of HNSCC cells. In an attempt to further elucidate how a tumour in its entity might respond to irradiation in regard to MAP kinase phosphorylation we analysed different tumour cell lines as well as normal and tumour-derived fibroblasts as an in vitro-tumour model. In this respect we investigated the ability of kinase inhibitor U0126 to suppress the irradiation (IR)-mediated cellular responses.
Methods: Irradiated cells were screened for pERK levels by Western blot followed by inhibitor treatment to compare the distinct responses of benign and malignant cell types. Functional analyses as proliferation assays and colony formation assays were performed to gain further insight into postradiogenic characteristics of the tumour model.
Results: Our data suggest that tumour-derived fibroblasts are much more resistant towards IR and pharmacological inhibition than tumour cells and normal fibroblasts, respectively. This might be due to the fact that these cells are conditioned by their tumour environment.
Conclusion: A closer insight into new combination treatment schemes is required to develop novel therapeutic approaches to overcome resistance mechanisms. Especially the role of tumour-derived fibroblasts needs to be evaluated in this respect.