title: Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas.
abstract: Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine angle. Significant clinical need exists for pharmacotherapies against VSs. Motivated by previous findings that immunohistochemical expression of cyclooxygenase 2 (COX-2) correlates with VS growth rate, we investigated the role of COX-2 in VSs and tested COX-2 inhibiting salicylates against VSs. COX-2 was found to be aberrantly expressed in human VS and primary human VS cells in comparison with control human nerve specimens and primary Schwann cells (SCs), respectively. Furthermore, levels of prostaglandin E2, the downstream enzymatic product of COX-2, were correlated with primary VS culture proliferation rate. Because COX-2 inhibiting salicylates such as aspirin are well tolerated and frequently clinically used, we assessed their repurposing for VS. Changes in proliferation, cell death, and cell viability were analyzed in primary VS cultures treated with aspirin, sodium salicylate, or 5-aminosalicylic acid. These drugs neither increased VS cell death nor affected healthy SCs. The cytostatic effect of aspirin in vitro was in concurrence with our previous clinical finding that patients with VS taking aspirin demonstrate reduced tumor growth. Overall, this work suggests that COX-2 is a key modulator in VS cell proliferation and survival and highlights salicylates as promising pharmacotherapies against VS.
authors.affiliation: Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Mass; Harvard-MIT Program in Speech and Hearing Bioscience and Technology, Cambridge, Mass.
authors.forename: Sonam
authors.initials: S
authors.lastname: Dilwali
authors.affiliation: Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Mass.
authors.forename: Shyan-Yuan
authors.initials: SY
authors.lastname: Kao
authors.affiliation: Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Mass; Department of Otology and Laryngology, Harvard Medical School, Boston, Mass.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Mass; Department of Otology and Laryngology, Harvard Medical School, Boston, Mass.
authors.forename: Lukas D
authors.initials: LD
authors.lastname: Landegger
authors.affiliation: Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Mass; Harvard-MIT Program in Speech and Hearing Bioscience and Technology, Cambridge, Mass; Department of Otology and Laryngology, Harvard Medical School, Boston, Mass. Electronic address: konstantina_stankovic@meei.harvard.edu.
authors.forename: Konstantina M
authors.initials: KM
authors.lastname: Stankovic
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D054697:Cytostatic Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019804:Mesalamine / Q000494:pharmacology; D009464:Neuroma, Acoustic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012980:Sodium Salicylate / Q000494:pharmacology; D057170:Translational Research, Biomedical; D014407:Tumor Cells, Cultured
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D054697:Cytostatic Agents; D019804:Mesalamine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone; D001241:Aspirin; D012980:Sodium Salicylate