gms | German Medical Science

Irradiation- stimulated signalling via the two pathways Raf-MEK-ERK and PI3K/Akt is known to be closely associated with a limited response to radiotherapy in HNSCC. In the present study, we have addressed the question whether the K-Ras mutation G12S causing constitutive activation of ERK and Akt is responsible for enhanced radioresistance in epithelial tumour cells.

We used two epithelial tumour cell lines as a model system, one of them harbouring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation (IR) and inhibitors on the expression of pERK and pAkt was determined by western blotting. Additionally clonogenic assays were performed to functionally analyse survival of the two different cell lines.

We observed the G12S cell line showing a clearly reduced response to inhibitor treatment under iradiation. We hypothesize a postradiogenic constitutive activation of the two pathways which are both required for Ras-mediated radioresistance in epithelial cells. If this effect should prove itself as a general mechanism in Ras-mutated tumours, application of specific inhibitors to block both cascades in parallel could contribute to enhance radiosensitivity in these types of cancer.