Sorafenib inhibits cell growth but fails to enhance radio- and chemosensitivity of glioblastoma cell lines
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Matthias Riedel1,*, Nina Struve1,*, Justus Müller-Goebel1, Sabrina Köcher1, Cordula Petersen1, Ekkehard Dikomey1, Kai Rothkamm1, Malte Kriegs1
1Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg – Eppendorf, Hubertus Wald Tumorzentrum – University Cancer Center Hamburg, 20246 Hamburg, Germany
*Matthias Riedel and Nina Struve share equal authorship
Nina Struve, email: [email protected]
Keywords: glioblastoma, sorafenib, X-irradiation, radiochemosensitivity, temozolomide
Received: December 18, 2015 Accepted: July 26, 2016 Published: August 17, 2016
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.
Conclusion: Our data suggest that sorafenib treatment may not improve the efficacy of radiochemotherapy in GBM.
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