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Turkish Journal of Biology

Abstract

Background: Glioblastoma (GBM) is a highly aggressive form of brain tumor characterized by rapid proliferation and invasiveness. It is associated with a poor prognosis due to acquired resistance to temozolomide (TMZ). In this study, we investigated whether a combination of epirubicin, 5-fluorouracil (5-FU), and TMZ could improve TMZ sensitivity in resistant GBM cells and help overcome resistance.Materials and methods: TMZ resistance was established in the U87MG cell line. The MTT assay was used to measure cell viability. Reactive oxygen species (ROS) and apoptosis were measured using flow cytometry. RNA-seq was used to evaluate genomic changes based on treatment with drugs alone or in combination. Results: We demonstrated that the triple-drug combination significantly reduced cell viability. The biochemical pathways involved revealed that this combination therapy significantly increased the generation of ROS. The RNA-seq analysis indicated that combination therapy effectively suppressed cell cycle regulatory pathways, enhancing cell cycle arrest and promoting apoptosis in TMZ-resistant cells. Conclusion: These findings underscore the potential viability of integrating epirubicin and 5-FU with TMZ to improve therapeutic outcomes in patients suffering from chemoresistant GBM. These combination therapies could represent an important advance in the treatment of this challenging malignancy.

Author ORCID Identifier

MEHRSA BAYAT: 0000-0003-2681-9500

MUHLİS AKMAN: 0000-0002-9350-9652

TÜRKER KILIÇ: 0000-0001-5982-9700

TİMUÇİN AVŞAR: 0000-0001-8841-4811

DOI

10.55730/1300-0152.2799

Keywords

Glioblastoma, chemoresistance, temozolomide, epirubicin, 5-fluorouracil, transcriptomics

First Page

170

Last Page

184

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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