Temozolomide treatment combined with AZD3463 shows synergistic effect in glioblastoma cells

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dc.contributor.authorGoker Bagca, B.
dc.contributor.authorOzates, N.P.
dc.contributor.authorAsik, A.
dc.contributor.authorCaglar, H.O.
dc.contributor.authorGunduz, C.
dc.contributor.authorBiray Avci, C.
dc.date.accessioned2020-12-01T11:52:47Z
dc.date.available2020-12-01T11:52:47Z
dc.date.issued2020
dc.departmentEge Üniversitesien_US
dc.description.abstractTemozolomide (TMZ) is used in the standard therapy regimen for patients with glioblastoma (GBM). However, some GBM patients do not respond to TMZ therapy. The combining therapeutic agents in GBM treatment are attracting considerable interest due to TMZ resistance. This study aims to identify the combinatorial effect of TMZ and AZD3463 on the viability of the T98G GBM cells. The cytotoxic effects of compounds were determined by using WST-8 assay. Flow cytometry was used to determine apoptosis and cell cycle profiles after treatments. Real-time PCR was used to identify mRNA expression of genes in the PI3K/AKT signaling pathway after treatments. IC50 concentrations of TMZ and AZD3463 were found to be 1.54 mM and 529 nM after incubation for 48 h, respectively. The combination treatment showed a synergistic effect on reducing the viability of GBM cells. Each one of TMZ, AZD3463, and combination treatments induced apoptosis. Treatments, either alone or the combination of these agents, caused the cell cycle arrest in distinct phases. TMZ and AZD3463 treatments, either alone or in combination, downregulated mRNA expression of genes in the PI3K/AKT signaling pathway. The combination of TMZ with AZD3463 may increase the efficacy of single TMZ treatment in GBM cells due to decreased expression of genes in the PI3K/AKT signaling pathway that is responsible for drug resistance and intratumoral heterogeneity. © 2020 Elsevier Inc.en_US
dc.identifier.doi10.1016/j.bbrc.2020.10.058
dc.identifier.issn0006-291X
dc.identifier.issn0006-291Xen_US
dc.identifier.pmid33109342en_US
dc.identifier.scopus2-s2.0-85094589406en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.bbrc.2020.10.058
dc.identifier.urihttps://hdl.handle.net/11454/61648
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofBiochemical and Biophysical Research Communicationsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectALK inhibitoren_US
dc.subjectAZD3463en_US
dc.subjectGlioblastomaen_US
dc.subjectTemozolomideen_US
dc.titleTemozolomide treatment combined with AZD3463 shows synergistic effect in glioblastoma cellsen_US
dc.typeArticleen_US

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