Open Access

Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide

  • Authors:
    • Thais Torquato Sales
    • Fernando Francisco Borges Resende
    • Natália Lemos Chaves
    • Simoneide Souza Titze-De-Almeida
    • Sônia Nair Báo
    • Marcella Lemos Brettas
    • Ricardo Titze‑De‑Almeida
  • View Affiliations

  • Published online on: August 10, 2016     https://doi.org/10.3892/ol.2016.4992
  • Pages: 2581-2589
  • Copyright: © Sales et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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October-2016
Volume 12 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Sales TT, Resende FF, Chaves NL, Titze-De-Almeida SS, Báo SN, Brettas ML and Titze‑De‑Almeida R: Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide. Oncol Lett 12: 2581-2589, 2016.
APA
Sales, T.T., Resende, F.F., Chaves, N.L., Titze-De-Almeida, S.S., Báo, S.N., Brettas, M.L., & Titze‑De‑Almeida, R. (2016). Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide. Oncology Letters, 12, 2581-2589. https://doi.org/10.3892/ol.2016.4992
MLA
Sales, T. T., Resende, F. F., Chaves, N. L., Titze-De-Almeida, S. S., Báo, S. N., Brettas, M. L., Titze‑De‑Almeida, R."Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide". Oncology Letters 12.4 (2016): 2581-2589.
Chicago
Sales, T. T., Resende, F. F., Chaves, N. L., Titze-De-Almeida, S. S., Báo, S. N., Brettas, M. L., Titze‑De‑Almeida, R."Suppression of the Eag1 potassium channel sensitizes glioblastoma cells to injury caused by temozolomide". Oncology Letters 12, no. 4 (2016): 2581-2589. https://doi.org/10.3892/ol.2016.4992