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PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells
Glioblastoma is the most common type of primary brain tumour in adults, and its pathogenesis is particularly complicated. Among the many possible mechanisms underlying its pathogenesis, hyperactivation of the PI3K/Akt pathway is essential to the occurrence and development of glioma through the loss...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278584/ https://www.ncbi.nlm.nih.gov/pubmed/30542720 http://dx.doi.org/10.3892/or.2018.6845 |
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author | Xu, Peng-Fei Yang, Ji-An Liu, Jun-Hui Yang, Xue Liao, Jian-Ming Yuan, Fan-En Liu, Bao-Hui Chen, Qian-Xue |
author_facet | Xu, Peng-Fei Yang, Ji-An Liu, Jun-Hui Yang, Xue Liao, Jian-Ming Yuan, Fan-En Liu, Bao-Hui Chen, Qian-Xue |
author_sort | Xu, Peng-Fei |
collection | PubMed |
description | Glioblastoma is the most common type of primary brain tumour in adults, and its pathogenesis is particularly complicated. Among the many possible mechanisms underlying its pathogenesis, hyperactivation of the PI3K/Akt pathway is essential to the occurrence and development of glioma through the loss of PTEN or somatic activating mutations in PIK3CA. In the present study, we investigated the effect of the PI3Kβ inhibitor AZD6482 on glioma cells. The CCK-8 assay showed dose-dependent cytotoxicity in glioma cell lines treated with AZD6482. Additionally, AZD6482 treatment was found to significantly induce apoptosis and cell cycle arrest as detected using flow cytometry. Moreover, as shown using western blot analysis, the levels of p-AKT, p-GSK-3β, Bcl-2, and cyclin D1 were decreased after AZD6482 treatment. In addition, we found that AZD6482 inhibited the migration and invasion of glioma cells as detected by wound healing and Transwell invasion assays. Taken together, our findings indicate that AZD6482 exerts an antitumour effect by inhibiting proliferation and inducing apoptosis in human glioma cells. AZD6482 may be applied as an adjuvant therapy to improve the therapeutic efficacy of glioblastoma treatment. |
format | Online Article Text |
id | pubmed-6278584 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-62785842018-12-17 PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells Xu, Peng-Fei Yang, Ji-An Liu, Jun-Hui Yang, Xue Liao, Jian-Ming Yuan, Fan-En Liu, Bao-Hui Chen, Qian-Xue Oncol Rep Articles Glioblastoma is the most common type of primary brain tumour in adults, and its pathogenesis is particularly complicated. Among the many possible mechanisms underlying its pathogenesis, hyperactivation of the PI3K/Akt pathway is essential to the occurrence and development of glioma through the loss of PTEN or somatic activating mutations in PIK3CA. In the present study, we investigated the effect of the PI3Kβ inhibitor AZD6482 on glioma cells. The CCK-8 assay showed dose-dependent cytotoxicity in glioma cell lines treated with AZD6482. Additionally, AZD6482 treatment was found to significantly induce apoptosis and cell cycle arrest as detected using flow cytometry. Moreover, as shown using western blot analysis, the levels of p-AKT, p-GSK-3β, Bcl-2, and cyclin D1 were decreased after AZD6482 treatment. In addition, we found that AZD6482 inhibited the migration and invasion of glioma cells as detected by wound healing and Transwell invasion assays. Taken together, our findings indicate that AZD6482 exerts an antitumour effect by inhibiting proliferation and inducing apoptosis in human glioma cells. AZD6482 may be applied as an adjuvant therapy to improve the therapeutic efficacy of glioblastoma treatment. D.A. Spandidos 2019-01 2018-11-02 /pmc/articles/PMC6278584/ /pubmed/30542720 http://dx.doi.org/10.3892/or.2018.6845 Text en Copyright: © Xu 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 Xu, Peng-Fei Yang, Ji-An Liu, Jun-Hui Yang, Xue Liao, Jian-Ming Yuan, Fan-En Liu, Bao-Hui Chen, Qian-Xue PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells |
title | PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells |
title_full | PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells |
title_fullStr | PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells |
title_full_unstemmed | PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells |
title_short | PI3Kβ inhibitor AZD6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells |
title_sort | pi3kβ inhibitor azd6482 exerts antiproliferative activity and induces apoptosis in human glioblastoma cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278584/ https://www.ncbi.nlm.nih.gov/pubmed/30542720 http://dx.doi.org/10.3892/or.2018.6845 |
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