The Dose Dependent Effects of Ruxolitinib on the Invasion and Tumorigenesis in Gliomas Cells via Inhibition of Interferon Gamma-Depended JAK/STAT Signaling Pathway

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dc.authorwosidDoğanlar, Oğuzhan/A-2315-2019
dc.contributor.authorDelen, Emre
dc.contributor.authorDoganlar, Oguzhan
dc.date.accessioned2024-06-12T11:13:47Z
dc.date.available2024-06-12T11:13:47Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description.abstractObjective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-alpha/IFN-beta receptor/STAT and IFN-gamma/IFN-gamma receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-alpha and IFN-gamma while no change on the hypoxia-inducible factor-1 alpha and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-alpha and IFN-gamma.en_US
dc.description.sponsorshipTrakya University Scientific Research [TUBAP-2018/155]; Turkish Neurosurgical Society, Ankara, Turkeyen_US
dc.description.sponsorshipThis research was supported by a grant from the Trakya University Scientific Research (TUBAP-2018/155). This study was supported by a grant from Turkish Neurosurgical Society, Ankara, Turkey.en_US
dc.identifier.doi10.3340/jkns.2019.0252
dc.identifier.endpage454en_US
dc.identifier.issn2005-3711
dc.identifier.issn1598-7876
dc.identifier.issue4en_US
dc.identifier.pmid32492985en_US
dc.identifier.scopus2-s2.0-85087571928en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage444en_US
dc.identifier.urihttps://doi.org/10.3340/jkns.2019.0252
dc.identifier.urihttps://hdl.handle.net/20.500.14551/23686
dc.identifier.volume63en_US
dc.identifier.wosWOS:000546353800005en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherKorean Neurosurgical Socen_US
dc.relation.ispartofJournal Of Korean Neurosurgical Societyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectRuxolitiniben_US
dc.subjectGlioblastomaen_US
dc.subjectCarcinogenesisen_US
dc.subjectInterferonsen_US
dc.subjectSignal Transductionen_US
dc.subjectAngiogenesisen_US
dc.subjectProliferationen_US
dc.subjectBetaen_US
dc.subjectVegfen_US
dc.titleThe Dose Dependent Effects of Ruxolitinib on the Invasion and Tumorigenesis in Gliomas Cells via Inhibition of Interferon Gamma-Depended JAK/STAT Signaling Pathwayen_US
dc.typeArticleen_US

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