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Essien, E.I. ; Hofer, T.P. ; Atkinson, M.J.* ; Anastasov, N.

Combining HDAC and MEK inhibitors with radiation against glioblastoma-derived spheres.

Cells 11:775 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Glioblastoma stem-like cells (GSLCs) in glioblastoma limit effective treatment and promote therapeutic resistance and tumor recurrence. Using a combined radiation and drugscreening platform, we tested the combination of a histone deacetylase inhibitor (HDACi) and MAPK/ERK kinase inhibitor (MEKi) with radiation to predict the efficacy against GSLCs. To mimic a stem-like phenotype, glioblastoma-derived spheres were used and treated with a combination of HDACi (MS-275) and MEKi (TAK-733 or trametinib) with 4 Gy irradiation. The sphere-forming ability after the combined radiochemotherapy was investigated using a sphere formation assay, while the expression levels of the GSLC markers (CD44, Nestin and SOX2) after treatment were analyzed using Western blotting and flow cytometry. The combined radiochemotherapy treatment inhibited the sphere formation in both glioblastoma-derived spheres, decreased the expression of the GSLC markers in a cell-line dependent manner and increased the dead cell population. Finally, we showed that the combined treatment with radiation was more effective at reducing the GSLC markers compared to the standard treatment of temozolomide and radiation. These results suggest that combining HDAC and MEK inhibition with radiation may offer a new strategy to improve the treatment of glioblastoma.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Combination Therapy ; Glioblastoma ; Glioblastoma-derived Spheres ; Hdac Inhibitor ; Mek Inhibitor ; Radiation; Cancer Stem-cells; Histone Deacetylase Inhibitors; Tumor-cells; Phase-i; Temozolomide; Identification; Expression; Sorafenib; Apoptosis; Blockade
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Journal Cells
Quellenangaben Volume: 11, Issue: 5, Pages: , Article Number: 775 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Institute(s) Institute of Biological and Medical Imaging (IBMI)
CF Immunoanalytics (IMA)
Institute of Radiation Biology (ISB)