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Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082

Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patients have a poor prognosis with a median survival of approximately 15 months despite the “Stupp” Regimen and high tumor recurrence due to the tumor resistance to chemotherapy. In this study, we co-cultured...

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Autores principales: Pustchi, Sadaf E., Avci, Naze G., Akay, Yasemin M., Akay, Metin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583902/
https://www.ncbi.nlm.nih.gov/pubmed/32998285
http://dx.doi.org/10.3390/ijms21197154
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author Pustchi, Sadaf E.
Avci, Naze G.
Akay, Yasemin M.
Akay, Metin
author_facet Pustchi, Sadaf E.
Avci, Naze G.
Akay, Yasemin M.
Akay, Metin
author_sort Pustchi, Sadaf E.
collection PubMed
description Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patients have a poor prognosis with a median survival of approximately 15 months despite the “Stupp” Regimen and high tumor recurrence due to the tumor resistance to chemotherapy. In this study, we co-cultured GBM cells with human astrocytes in three-dimensional (3D) poly(ethylene glycol) dimethyl acrylate (PEGDA) microwells to mimic the tumor microenvironment. We treated 3D co- and mono-cultured cells with Temozolomide (TMZ) and the nuclear factor-κB (NF-κB) inhibitor Bay 11-7082 and investigated the combined effect of the drugs. We assessed the expressions of glial fibrillary acidic protein (GFAP) and vimentin that play a role in the tumor malignancy and activation of the astrocytes as well as Notch-1 and survivin that play a role in GBM malignancy after the drug treatment to understand how astrocytes induced GBM drug response. Our results showed that in the co-culture, astrocytes increased GBM survival and resistance after combined drug treatment compared to mono-cultures. These data restated the importance of 3D cell culture to mimic the tumor microenvironment for drug screening.
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spelling pubmed-75839022020-10-29 Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082 Pustchi, Sadaf E. Avci, Naze G. Akay, Yasemin M. Akay, Metin Int J Mol Sci Article Glioblastoma multiforme (GBM) is the most common malignant type of astrocytic tumors. GBM patients have a poor prognosis with a median survival of approximately 15 months despite the “Stupp” Regimen and high tumor recurrence due to the tumor resistance to chemotherapy. In this study, we co-cultured GBM cells with human astrocytes in three-dimensional (3D) poly(ethylene glycol) dimethyl acrylate (PEGDA) microwells to mimic the tumor microenvironment. We treated 3D co- and mono-cultured cells with Temozolomide (TMZ) and the nuclear factor-κB (NF-κB) inhibitor Bay 11-7082 and investigated the combined effect of the drugs. We assessed the expressions of glial fibrillary acidic protein (GFAP) and vimentin that play a role in the tumor malignancy and activation of the astrocytes as well as Notch-1 and survivin that play a role in GBM malignancy after the drug treatment to understand how astrocytes induced GBM drug response. Our results showed that in the co-culture, astrocytes increased GBM survival and resistance after combined drug treatment compared to mono-cultures. These data restated the importance of 3D cell culture to mimic the tumor microenvironment for drug screening. MDPI 2020-09-28 /pmc/articles/PMC7583902/ /pubmed/32998285 http://dx.doi.org/10.3390/ijms21197154 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pustchi, Sadaf E.
Avci, Naze G.
Akay, Yasemin M.
Akay, Metin
Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082
title Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082
title_full Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082
title_fullStr Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082
title_full_unstemmed Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082
title_short Astrocytes Decreased the Sensitivity of Glioblastoma Cells to Temozolomide and Bay 11-7082
title_sort astrocytes decreased the sensitivity of glioblastoma cells to temozolomide and bay 11-7082
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583902/
https://www.ncbi.nlm.nih.gov/pubmed/32998285
http://dx.doi.org/10.3390/ijms21197154
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