期刊
JOURNAL OF ORAL PATHOLOGY & MEDICINE
卷 42, 期 8, 页码 612-619出版社
WILEY
DOI: 10.1111/jop.12056
关键词
head and neck squamous cell carcinoma; irradiation; MAP kinase pathway; reactive oxygen species; vascular endothelial growth factor
资金
- Foundation Head and Neck Tumor Research, Wiesbaden, Germany
BACKGROUND: Radioresistance limits the effectiveness of radiotherapy in head and neck squamous cell carcinoma. We previously demonstrated post-radiogenic mitogen-activated protein kinase (MAPK) pathway activation and vascular endothelial growth factor (VEGF) release resulting in reduced tumor cell response. Here, we examined the association of this mechanism with the induction of reactive oxygen species (ROS) under irradiation (IR). METHODS: Intracellular ROS after IR were measured. We modeled radiation-induced ROS by exposure of two SCC lines to H2O2 and evaluated the impact of irradiation and ROS on ERK phosphorylation by Western blot, immunohistochemistry, and ELISA. RESULTS: We found elevated pERK levels after treatment with IR and H2O2, which could be distinctly suppressed by U0126. Immunohistochemistry and ELISA revealed increased intracellular VEGF levels after H2O2 application. CONCLUSIONS: Our data show that irradiation-induced ROS activate the MAPK pathway and release of VEGF. As VEGF is known to be released after cellular distress resulting in cytoprotection, the described mechanism is potentially of importance for therapy success.
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