Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2
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Benjamin M. Wahle1,2, Eric T. Hawley1, Yongzheng He1, Abbi E. Smith1, Jin Yuan1, Andi R. Masters3, David R. Jones3, Jeffrey R. Gehlhausen1, Su-Jung Park1, Simon J. Conway1, D. Wade Clapp1 and Charles W. Yates1,2
1Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
2Department of Otolaryngology/Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
3Clinical Pharmacology Analytical Core, Indiana University Simon Cancer Center, Indianapolis, Indiana, USA
D. Wade Clapp, email: [email protected]
Charles W. Yates, email: [email protected]
Keywords: neurofibromatosis type 2; vestibular schwannoma; cyclooxygenase 2; non-steroidal anti-inflammatory agents; transgenic mice
Abbreviations: COX-2 (cyclooxygenase-2), NSAID (nonsteroidal antiinflamatory drug)
Received: March 31, 2017 Accepted: October 02, 2017 Published: October 24, 2017
Mutations in the tumor suppressor gene NF2 lead to Neurofibromatosis type 2 (NF2), a tumor predisposition syndrome characterized by the development of schwannomas, including bilateral vestibular schwannomas with complete penetrance. Recent work has implicated the importance of COX-2 in schwannoma growth. Using a genetically engineered murine model of NF2, we demonstrate that selective inhibition of COX-2 with celecoxib fails to prevent the spontaneous development of schwannomas or sensorineural hearing loss in vivo, despite elevated expression levels of COX-2 in Nf2-deficient tumor tissue. These results suggest that COX-2 is nonessential to schwannomagenesis and that the proposed tumor suppressive effects of NSAIDs on schwannomas may occur through COX-2 independent mechanisms.
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