Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response. (11th March 2013)

• Record Type: Journal Article
• Authors: Drigotas, Martynas; Affolter, Annette; Mann, Wolf J.; Brieger, Juergen
• Is Part Of: Journal of oral pathology & medicine. Volume 42:Number 8(2013:Sep.)
• Page Start: 612
• Page End: 619
• Publication Date: 2013-03-11
• Subjects: Dentistry -- Periodicals; Teeth -- Diseases -- Periodicals; 617
• DOI: 10.1111/jop.12056
• Languages: English
• ISSNs: 0904-2512

Abstract

<abstract abstract-type="main" xml:lang="en" id="jop12056-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jop12056-sec-0001" sec-type="section"> <title>Background</title> <p>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).</p> </sec> <sec id="jop12056-sec-0002" sec-type="section"> <title>Methods</title> <p>Intracellular ROS after IR were measured. We modeled radiation‐induced ROS by exposure of two SCC lines to H<sub>2</sub>O<sub>2</sub> and evaluated the impact of irradiation and ROS on ERK phosphorylation by Western blot, immunohistochemistry, and ELISA.</p> </sec> <sec id="jop12056-sec-0003" sec-type="section"> <title>Results</title> <p>We found elevated pERK levels after treatment with IR and H<sub>2</sub>O<sub>2</sub>, which could be distinctly suppressed by U0126. Immunohistochemistry and ELISA revealed increased intracellular VEGF levels after H<sub>2</sub>O<sub>2</sub> application.</p> </sec> <sec id="jop12056-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>