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Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474)
Proteasome inhibitors have been proven to be effective anticancer compounds in many tumor models, including glioblastoma multiforme (GBM). In this study, we found that the proteasome inhibitor Velcade (PS-341/bortezomib) caused GBM cell death while simultaneously activating the PI3K/Akt pathway. The...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898871/ https://www.ncbi.nlm.nih.gov/pubmed/24297065 http://dx.doi.org/10.3892/ijo.2013.2205 |
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author | LIN, LEHANG GAUT, DARIA HU, KAISHUN YAN, HAIYAN YIN, DONG KOEFFLER, H. PHILLIP |
author_facet | LIN, LEHANG GAUT, DARIA HU, KAISHUN YAN, HAIYAN YIN, DONG KOEFFLER, H. PHILLIP |
author_sort | LIN, LEHANG |
collection | PubMed |
description | Proteasome inhibitors have been proven to be effective anticancer compounds in many tumor models, including glioblastoma multiforme (GBM). In this study, we found that the proteasome inhibitor Velcade (PS-341/bortezomib) caused GBM cell death while simultaneously activating the PI3K/Akt pathway. Therefore, we sought to investigate if the PI3K inhibitor ZSTK474 would enhance the effectiveness of Velcade in anticancer therapy. Two GBM cell lines were used to detect the effects of Velcade and ZSTK474 alone or in combination in vitro. The combination of Velcade and ZSTK474 synergistically inhibited the proliferation of GBM cell lines. Cell apoptosis was increased when exposed to Velcade and ZSTK474 in combination as shown by Annexin V analysis. Treatment with both drugs led to downregulation of the p-Akt, p-4EBP1 and p-mTOR proteins as determined by western blot analysis. The anticancer ability of Velcade for glioblastoma multiforme was, therefore, enhanced by combination with the PI3K pathway inhibitor ZSTK474 in glioblastoma multiforme. |
format | Online Article Text |
id | pubmed-3898871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-38988712014-01-24 Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474) LIN, LEHANG GAUT, DARIA HU, KAISHUN YAN, HAIYAN YIN, DONG KOEFFLER, H. PHILLIP Int J Oncol Articles Proteasome inhibitors have been proven to be effective anticancer compounds in many tumor models, including glioblastoma multiforme (GBM). In this study, we found that the proteasome inhibitor Velcade (PS-341/bortezomib) caused GBM cell death while simultaneously activating the PI3K/Akt pathway. Therefore, we sought to investigate if the PI3K inhibitor ZSTK474 would enhance the effectiveness of Velcade in anticancer therapy. Two GBM cell lines were used to detect the effects of Velcade and ZSTK474 alone or in combination in vitro. The combination of Velcade and ZSTK474 synergistically inhibited the proliferation of GBM cell lines. Cell apoptosis was increased when exposed to Velcade and ZSTK474 in combination as shown by Annexin V analysis. Treatment with both drugs led to downregulation of the p-Akt, p-4EBP1 and p-mTOR proteins as determined by western blot analysis. The anticancer ability of Velcade for glioblastoma multiforme was, therefore, enhanced by combination with the PI3K pathway inhibitor ZSTK474 in glioblastoma multiforme. D.A. Spandidos 2013-12-02 /pmc/articles/PMC3898871/ /pubmed/24297065 http://dx.doi.org/10.3892/ijo.2013.2205 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles LIN, LEHANG GAUT, DARIA HU, KAISHUN YAN, HAIYAN YIN, DONG KOEFFLER, H. PHILLIP Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474) |
title | Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474) |
title_full | Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474) |
title_fullStr | Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474) |
title_full_unstemmed | Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474) |
title_short | Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474) |
title_sort | dual targeting of glioblastoma multiforme with a proteasome inhibitor (velcade) and a phosphatidylinositol 3-kinase inhibitor (zstk474) |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898871/ https://www.ncbi.nlm.nih.gov/pubmed/24297065 http://dx.doi.org/10.3892/ijo.2013.2205 |
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