Notch1 and Major Vault Proteins Modulate Temozolomide Resistance in Glioblastoma
Küçük Resim Yok
Tarih
2025
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
The 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.
Açıklama
Anahtar Kelimeler
glioblastoma multiforme, major vault protein, notch, temozolomide
Kaynak
Journal of Cellularand Molecular Medicine
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
29
Sayı
6
