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Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide
Glioblastoma multiforme (GBM) is the most aggressive type of human primary brain tumor. The standard treatment protocol includes radiotherapy in combination with temozolomide (TMZ). Despite advances in GBM treatment, the survival time of patients diagnosed with glioma is 14.5 months. Regarding tumor...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038559/ https://www.ncbi.nlm.nih.gov/pubmed/27698831 http://dx.doi.org/10.3892/ol.2016.4992 |
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author | Sales, Thais Torquato Resende, Fernando Francisco Borges Chaves, Natália Lemos Titze-De-Almeida, Simoneide Souza Báo, Sônia Nair Brettas, Marcella Lemos Titze-De-Almeida, Ricardo |
author_facet | Sales, Thais Torquato Resende, Fernando Francisco Borges Chaves, Natália Lemos Titze-De-Almeida, Simoneide Souza Báo, Sônia Nair Brettas, Marcella Lemos Titze-De-Almeida, Ricardo |
author_sort | Sales, Thais Torquato |
collection | PubMed |
description | Glioblastoma multiforme (GBM) is the most aggressive type of human primary brain tumor. The standard treatment protocol includes radiotherapy in combination with temozolomide (TMZ). Despite advances in GBM treatment, the survival time of patients diagnosed with glioma is 14.5 months. Regarding tumor biology, various types of cancer cell overexpress the ether à go-go 1 (Eag1) potassium channel. Therefore, the present study examined the role of Eag1 in the cell damage caused by TMZ on the U87MG glioblastoma cell line. Eag1 was inhibited using a channel blocker (astemizole) or silenced by a short-hairpin RNA expression vector (pKv10.1-3). pKv10.1-3 (0.2 µg) improved the Eag1 silencing caused by 250 µM TMZ, as determined by reverse transcription-quantitative polymerase chain reaction and immunocytochemistry. Additionally, inhibiting Eag1 with the vector or astemizole (5 µM) reduced glioblastoma cell viability and sensitized cells to TMZ. Cell viability decreased by 63% for pKv10.1-3 + TMZ compared with 34% for TMZ alone, and by 77% for astemizole + TMZ compared with 46% for TMZ alone, as determined by MTT assay. In addition, both the vector and astemizole increased the apoptosis rate of glioblastoma cells triggered by TMZ, as determined by an Annexin V apoptosis assay. Collectively, the current data reveal that Eag1 has a role in the damage caused to glioblastoma by TMZ. Furthermore, suppression of this channel can improve the action of TMZ on U87MG glioblastoma cells. Thus, silencing Eag1 is a promising strategy to improve GBM treatment and merits additional studies in animal models of glioma. |
format | Online Article Text |
id | pubmed-5038559 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-50385592016-10-03 Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide Sales, Thais Torquato Resende, Fernando Francisco Borges Chaves, Natália Lemos Titze-De-Almeida, Simoneide Souza Báo, Sônia Nair Brettas, Marcella Lemos Titze-De-Almeida, Ricardo Oncol Lett Articles Glioblastoma multiforme (GBM) is the most aggressive type of human primary brain tumor. The standard treatment protocol includes radiotherapy in combination with temozolomide (TMZ). Despite advances in GBM treatment, the survival time of patients diagnosed with glioma is 14.5 months. Regarding tumor biology, various types of cancer cell overexpress the ether à go-go 1 (Eag1) potassium channel. Therefore, the present study examined the role of Eag1 in the cell damage caused by TMZ on the U87MG glioblastoma cell line. Eag1 was inhibited using a channel blocker (astemizole) or silenced by a short-hairpin RNA expression vector (pKv10.1-3). pKv10.1-3 (0.2 µg) improved the Eag1 silencing caused by 250 µM TMZ, as determined by reverse transcription-quantitative polymerase chain reaction and immunocytochemistry. Additionally, inhibiting Eag1 with the vector or astemizole (5 µM) reduced glioblastoma cell viability and sensitized cells to TMZ. Cell viability decreased by 63% for pKv10.1-3 + TMZ compared with 34% for TMZ alone, and by 77% for astemizole + TMZ compared with 46% for TMZ alone, as determined by MTT assay. In addition, both the vector and astemizole increased the apoptosis rate of glioblastoma cells triggered by TMZ, as determined by an Annexin V apoptosis assay. Collectively, the current data reveal that Eag1 has a role in the damage caused to glioblastoma by TMZ. Furthermore, suppression of this channel can improve the action of TMZ on U87MG glioblastoma cells. Thus, silencing Eag1 is a promising strategy to improve GBM treatment and merits additional studies in animal models of glioma. D.A. Spandidos 2016-10 2016-08-10 /pmc/articles/PMC5038559/ /pubmed/27698831 http://dx.doi.org/10.3892/ol.2016.4992 Text en Copyright: © Sales et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Sales, Thais Torquato Resende, Fernando Francisco Borges Chaves, Natália Lemos Titze-De-Almeida, Simoneide Souza Báo, Sônia Nair Brettas, Marcella Lemos Titze-De-Almeida, Ricardo Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide |
title | Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide |
title_full | Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide |
title_fullStr | Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide |
title_full_unstemmed | Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide |
title_short | Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide |
title_sort | suppression of the eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038559/ https://www.ncbi.nlm.nih.gov/pubmed/27698831 http://dx.doi.org/10.3892/ol.2016.4992 |
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