Affiliation:
1. Department of Medical Biology, Medical Faculty, Ege University, Bornova, 35100, Izmir, Turkey
2. Department of Stem Cell, Health Science Institute, Ege University, Bornova, 35100, Izmir, Turkey
Abstract
Background:
Salinomycin, an ionophore antibiotic, is known to be an effective agent in reducing the
viability of Glioblastoma (GBM) cells. The combination of salinomycin with other chemotherapeutic drugs
would help to overcome the drug resistance of GBM cells.
Objective:
This study aims to test the combinatorial effect of salinomycin and AZD3463 in T98G GBM cells.
Methods:
The cytotoxic effects of drugs on T98G GBM cells were determined by using WST-8 assay. Flow
cytometry was used to identify apoptosis and cell cycle profiles after treatments. Real-time PCR was used to
portray mRNA expression profiles of genes in the Wnt-signaling pathway after treatments.
Results:
IC50 concentrations of AZD3463 and salinomycin were 529nM and 7.3μM for 48h, respectively. The
combination concentrations of AZD3463 and salinomycin were 3.3μM and 333nM, respectively. The combination
treatment showed a synergistic effect on reducing the viability of GBM cells. AZD3463, salinomycin, and
their combination induced apoptosis in 1.2, 1.4, and 3.2 folds, respectively. AZD3463 and the combination
treatment induced the cell cycle arrest at the G1 phase. Salinomycin and AZD3463 treatments, either alone or in
combination, resulted in the downregulation or upregulation of mRNA expression levels of genes in the Wntsignaling
pathway.
Conclusion:
Salinomycin, AZD3463, and their combination may inhibit proliferation and induce apoptosis in
GBM cells due to a decrease in expression levels of genes acting in both the canonical and non-canonical Wnt
signaling pathways. The Wnt signaling pathway may be involved in salinomycin-AZD3463 drug interaction.
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Pharmacology,Molecular Medicine
Cited by
2 articles.
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