Article
In vitro-analysis of sorafenib as a radiosensitizing agent in epithelial cancer
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Published: | July 23, 2012 |
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Background: Tumours of epithelial origin frequently develop resistance towards irradiation. We have recently shown that the ionizing radiation (IR)- activated MAPK pathway is involved in the survival of resistant neoplasms. We now examined if treatment with sorafenib, a potent multikinase inhibitor of IR- activated signalling factors, could act as a radiosensitizing agent.
Methods: Epithelial tumour cell lines from the head and neck (HNSCCUM-01T; UM-SCC-33) and from the lung (A549) were chosen. Cultured cell lines were treated with sorafenib and subsequently irradiated with 0, 4, and 50 Gy. The apoptotic response to IR and inhibitor treatment was evaluated by annexin-V apoptosis assay.
Results: Combination treatment synergistically enhanced apoptosis already at a minor dose of 4 Gy. Especially cell lines HNSCCUM-01T and A549 displayed a strong decrease of cellular survival. Compared to the apoptotic rate, necrotic rates were less influenced by combination treatment moreover simply displaying additive effects.
Conclusion: Taken together, our results suggest a new role of clinically yet established kinase inhibitor sorafenib as a radiosensitizing agent in epithelial cancer. Hence, quantification of apoptosis in tumour biopsies could represent a novel monitoring tool for successful therapeutic approaches in this regard.