title: Effect of sorafenib on cisplatin-based chemoradiation in head and neck cancer cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Möckelmann
authors.affiliation: 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.|Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Rieckmann
authors.affiliation: 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.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Busch
authors.affiliation: 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.|Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Becker
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gleißner
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Hoffer
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Omniczynski
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Steinmeister
authors.affiliation: 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.|Department of Otorhinolaryngology and Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Laban
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery and Department of Medical Biochemistry and Genetics, Turku University and University Hospital of Turku, Turku, Finland.
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Rothkamm
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Department of Radiotherapy and Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dikomey
authors.affiliation: 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.
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
authors.affiliation: Head and Neck Cancer Center of The University Cancer Center Hamburg (UCCH), Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kriegs
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077157:Sorafenib; D014407:Tumor Cells, Cultured; D014965:X-Rays
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011838:Radiation-Sensitizing Agents; D009536:Niacinamide; D000077157:Sorafenib; D002945:Cisplatin
keywords: HNSCC; cisplatin; molecular targeting; radiosensitization; sorafenib