title: Sorafenib inhibits cell growth but fails to enhance radio- and chemosensitivity of glioblastoma cell lines.
abstract: BACKGROUND
  Glioblastomas (GBM) are the most common malignant type of primary brain tumor. GBM are intensively treated with surgery and combined radiochemotherapy using X-irradiation and temozolomide (TMZ) but they are still associated with an extremely poor prognosis, urging for the development of new treatment strategies. To improve the outcome of GBM patients, the small molecule multi-kinase inhibitor sorafenib has moved into focus of recent research. Sorafenib has already been shown to enhance the radio- and radiochemosensitivity of other tumor entities. Whether sorafenib is also able to sensitize GBM cells to radio- and chemotherapy is still an unsolved question which we have addressed in this study.
  
  
  METHODS
  The effect of sorafenib on signaling, proliferation, radiosensitivity, chemosensitivity and radiochemosensitivity was analyzed in six glioblastoma cell lines using Western blot, proliferation- and colony formation assays.
  
  
  RESULTS
  In half of the cell lines sorafenib clearly inhibited MAPK signaling. We also observed a strong blockage of proliferation, which was, however, not associated with MAPK pathway inhibition. Sorafenib had only minor effects on cell survival when administered alone. Most importantly, sorafenib treatment failed to enhance GBM cell killing by irradiation, TMZ or combined treatment, and instead rather caused resistance in some cell lines.
  
  
  CONCLUSIONS
  Our data suggest that sorafenib treatment may not improve the efficacy of radiochemotherapy in GBM.
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Riedel
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Struve
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Justus
authors.initials: J
authors.lastname: Müller-Goebel
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Köcher
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dikomey
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Rothkamm
authors.affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg - Eppendorf, Hubertus Wald Tumorzentrum - University Cancer Center Hamburg, 20246 Hamburg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kriegs
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D020935:MAP Kinase Signaling System; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011836:Radiation Tolerance; D015398:Signal Transduction; D000077157:Sorafenib; D014965:X-Rays
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: X-irradiation; glioblastoma; radiochemosensitivity; sorafenib; temozolomide