Sorafenib sensitizes head and neck squamous cell carcinoma cells to ionizing radiation
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Sorafenib sensitizes head and neck squamous cell carcinoma cells to ionizing radiation. / Laban, Simon; Steinmeister, Leonhard; Gleißner, Lisa; Grob, Tobias J; Grénman, Reidar; Petersen, Cordula; Gal, Andreas; Knecht, Rainald; Dikomey, Ekkehard; Kriegs, Malte.
In: RADIOTHER ONCOL, Vol. 109, No. 2, 01.11.2013, p. 286-92.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Sorafenib sensitizes head and neck squamous cell carcinoma cells to ionizing radiation
AU - Laban, Simon
AU - Steinmeister, Leonhard
AU - Gleißner, Lisa
AU - Grob, Tobias J
AU - Grénman, Reidar
AU - Petersen, Cordula
AU - Gal, Andreas
AU - Knecht, Rainald
AU - Dikomey, Ekkehard
AU - Kriegs, Malte
N1 - Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - BACKGROUND AND PURPOSE: There is a great need to improve the outcome of locoregionally advanced squamous cell carcinomas of the head and neck (HNSCC). Standard treatment includes a combination of surgery, radio- and chemotherapy. The addition of molecular targeting agents to conventional treatment may improve outcomes. In this study the Raf inhibitor sorafenib was used to increase the radiosensitivity of HNSCC cell lines.MATERIAL AND METHODS: In a panel of six cell lines (A549, FaDu, UTSCC 60A, UTSCC 42A, UTSCC 42B, UTSCC 29) radiosensitivity was measured by colony formation assay and apoptosis and cell cycle analysis were performed by flow cytometry. DNA repair was analyzed by 53BP1 immunohistochemistry.RESULTS: Sorafenib added prior to irradiation resulted in an increased cellular radiosensitivity (DEF0.5=1.11-1.84). Radiosensitization was not caused by an enhanced rate of apoptosis or cell cycle effects. In contrast, sorafenib was shown for the first time to block the repair of DNA double-strand breaks (DSB).CONCLUSION: Our data suggest that sorafenib may be used to overcome the radioresistance of HNSCC through the inhibition of DSB repair.
AB - BACKGROUND AND PURPOSE: There is a great need to improve the outcome of locoregionally advanced squamous cell carcinomas of the head and neck (HNSCC). Standard treatment includes a combination of surgery, radio- and chemotherapy. The addition of molecular targeting agents to conventional treatment may improve outcomes. In this study the Raf inhibitor sorafenib was used to increase the radiosensitivity of HNSCC cell lines.MATERIAL AND METHODS: In a panel of six cell lines (A549, FaDu, UTSCC 60A, UTSCC 42A, UTSCC 42B, UTSCC 29) radiosensitivity was measured by colony formation assay and apoptosis and cell cycle analysis were performed by flow cytometry. DNA repair was analyzed by 53BP1 immunohistochemistry.RESULTS: Sorafenib added prior to irradiation resulted in an increased cellular radiosensitivity (DEF0.5=1.11-1.84). Radiosensitization was not caused by an enhanced rate of apoptosis or cell cycle effects. In contrast, sorafenib was shown for the first time to block the repair of DNA double-strand breaks (DSB).CONCLUSION: Our data suggest that sorafenib may be used to overcome the radioresistance of HNSCC through the inhibition of DSB repair.
U2 - 10.1016/j.radonc.2013.07.003
DO - 10.1016/j.radonc.2013.07.003
M3 - SCORING: Journal article
C2 - 23953412
VL - 109
SP - 286
EP - 292
JO - RADIOTHER ONCOL
JF - RADIOTHER ONCOL
SN - 0167-8140
IS - 2
ER -