Effect of sorafenib on cisplatin-based chemoradiation in head and neck cancer cells
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Effect of sorafenib on cisplatin-based chemoradiation in head and neck cancer cells. / Möckelmann, Nikolaus; Rieckmann, Thorsten; Busch, Chia-Jung; Becker, Benjamin; Gleißner, Lisa; Hoffer, Konstantin; Omniczynski, Maria; Steinmeister, Leonhard; Laban, Simon; Grénman, Reidar; Petersen, Cordula; Rothkamm, Kai; Dikomey, Ekkehard; Knecht, Rainald; Kriegs, Malte.
in: ONCOTARGET, Jahrgang 7, Nr. 17, 26.04.2016, S. 23542-51.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Effect of sorafenib on cisplatin-based chemoradiation in head and neck cancer cells
AU - Möckelmann, Nikolaus
AU - Rieckmann, Thorsten
AU - Busch, Chia-Jung
AU - Becker, Benjamin
AU - Gleißner, Lisa
AU - Hoffer, Konstantin
AU - Omniczynski, Maria
AU - Steinmeister, Leonhard
AU - Laban, Simon
AU - Grénman, Reidar
AU - Petersen, Cordula
AU - Rothkamm, Kai
AU - Dikomey, Ekkehard
AU - Knecht, Rainald
AU - Kriegs, Malte
PY - 2016/4/26
Y1 - 2016/4/26
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.18632/oncotarget.8275
DO - 10.18632/oncotarget.8275
M3 - SCORING: Journal article
C2 - 27015558
VL - 7
SP - 23542
EP - 23551
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 17
ER -
