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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...

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Autores principales: Xu, Peng-Fei, Yang, Ji-An, Liu, Jun-Hui, Yang, Xue, Liao, Jian-Ming, Yuan, Fan-En, Liu, Bao-Hui, Chen, Qian-Xue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
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.
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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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