Notch1 and Major Vault Proteins Modulate Temozolomide Resistance in Glioblastoma

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dc.authoridtuncer, cengiz/0000-0003-2400-5546
dc.authoridHacioglu, Ceyhan/0000-0002-0993-6118
dc.contributor.authorTuncer, Cengiz
dc.contributor.authorHacioglu, Ceyhan
dc.date.accessioned2025-10-11T20:48:13Z
dc.date.available2025-10-11T20:48:13Z
dc.date.issued2025
dc.departmentDüzce Üniversitesien_US
dc.description.abstractThe development of resistance to chemotherapy in the case of aggressive glioblastoma multiforme (GBM) presents a significant treatment challenge. Dysregulation of the Notch signalling pathway promotes tumour proliferation in GBM cells. This study was that targeting the Notch signalling pathway could be a potential therapeutic approach for GBM. Initially, temozolomide-(TMZ)-resistant GBM cells were generated, and the effect of Notch1 on the expression of multiple resistance proteins within these cells was investigated. Subsequently, the expression of Notch-1 in GBM cells was reduced using siRNA. Results revealed a significant reduction in TMZ sensitivity in TMZ-resistant GBM cells, accompanied by a substantial increase in the expression of major vault protein-(MVP), O6-methylguanine-DNA-methyltransferase-(MGMT), and ATP-binding-cassette transporter-G2-(ABCG2). Furthermore, TMZ-resistant U87-R and U251-R cells exhibited higher proliferation rates compared to their parental control cells (U87 and U251). Additionally, we observed that downregulating Notch-1 signalling inhibited the proliferation of TMZ-resistant U87-R and U251-R cells. This downregulation led to the inactivation of MGMT, ABCG2, and MVP. Importantly, it increased chemosensitivity to TMZ, particularly by downregulating MVP expression. Consequently, Notch1 could serve as a potential therapeutic target for GBM cells and may be effective in preventing TMZ resistance by targeting MVP, as well as MGMT and ABCG2 in GBM cells.en_US
dc.identifier.doi10.1111/jcmm.70474
dc.identifier.issn1582-1838
dc.identifier.issn1582-4934
dc.identifier.issue6en_US
dc.identifier.pmid40100070en_US
dc.identifier.scopus2-s2.0-105000806793en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1111/jcmm.70474
dc.identifier.urihttps://hdl.handle.net/20.500.12684/21813
dc.identifier.volume29en_US
dc.identifier.wosWOS:001446882800001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofJournal of Cellularand Molecular Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectglioblastoma multiformeen_US
dc.subjectmajor vault proteinen_US
dc.subjectnotchen_US
dc.subjecttemozolomideen_US
dc.titleNotch1 and Major Vault Proteins Modulate Temozolomide Resistance in Glioblastomaen_US
dc.typeArticleen_US

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