Effect of sorafenib on cisplatin-based chemoradiation in head and neck cancer cells
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Nikolaus Möckelmann1, Thorsten Rieckmann1,2, Chia-Jung Busch1, Benjamin Becker1,2, Lisa Gleißner2, Konstantin Hoffer2, Maria Omniczynski2, Leonhard Steinmeister2, Simon Laban1,5, Reidar Grénman3, Cordula Petersen4, Kai Rothkamm2, Ekkehard Dikomey2,4, Rainald Knecht1 and Malte Kriegs2
1 Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2 Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3 Department of Otorhinolaryngology – Head and Neck Surgery and Department of Medical Biochemistry and Genetics, Turku University and University Hospital of Turku, Turku, Finland
4 Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
5 Department of Otorhinolaryngology and Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany
Nikolaus Möckelmann , email:
Keywords: HNSCC, sorafenib, molecular targeting, radiosensitization, cisplatin
Received: January 23, 2016 Accepted: March 01, 2016 Published: March 22, 2016
Despite aggressive chemoradiation (CRT) protocols in the treatment of patients with head and neck squamous cell carcinomas (HNSCC), the outcome is still unfavorable. To improve therapy efficacy we had already successfully tested the multikinase inhibitor sorafenib in combination with irradiation (IR) in previous studies on HNSCC cell lines. In this study we investigated its effect on combined CRT treatment using cisplatin.Radio- and chemosensitivity with and without sorafenib was measured in four HNSCC cell lines and normal fibroblasts (NF) by colony formation assay. Apoptosis and cell cycle analysis were performed by flow cytometry.
In HNSCC cells, sorafenib enhanced the antiproliferative effect of cisplatin without affecting apoptosis induction and with only minor effects on cell inactivation. Sorafenib added prior to irradiation enhanced cellular radiosensitivity in three of the tested HNSCC cell lines and caused massive overall cell inactivation when combined with CRT. In contrast, sorafenib did not radiosensitize NF and reduced cisplatin-induced cell inactivation. Cell inactivation by IR and cisplatin is further increased by the addition of sorafenib in HNSCC, but not in NF cells. Therefore, sorafenib is a promising candidate to improve therapy efficacy for HNSCC.
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