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Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer

BACKGROUND: Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays an important role in cancer tumorigenesis and progression. We investigated the role of the GSK-3β inhibitor AZD1080 in ovarian cancer cell lines. METHODS: A2780 and OVCAR3 ovarian cancer cell lin...

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Autores principales: Chen, Shuo, Sun, Kai-Xuan, Feng, Miao-Xiao, Sang, Xiu-Bo, Liu, Bo-Liang, Zhao, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807899/
https://www.ncbi.nlm.nih.gov/pubmed/27051274
http://dx.doi.org/10.2147/DDDT.S102506
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author Chen, Shuo
Sun, Kai-Xuan
Feng, Miao-Xiao
Sang, Xiu-Bo
Liu, Bo-Liang
Zhao, Yang
author_facet Chen, Shuo
Sun, Kai-Xuan
Feng, Miao-Xiao
Sang, Xiu-Bo
Liu, Bo-Liang
Zhao, Yang
author_sort Chen, Shuo
collection PubMed
description BACKGROUND: Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays an important role in cancer tumorigenesis and progression. We investigated the role of the GSK-3β inhibitor AZD1080 in ovarian cancer cell lines. METHODS: A2780 and OVCAR3 ovarian cancer cell lines were exposed to AZD1080, after which cell proliferation, cell cycle, invasion, and migration assays were performed. Phalloidin staining was used to observe lamellipodia formation. Reverse transcription polymerase chain reaction and Western blot were used to assess the respective mRNA and protein expression levels of GSK-3β, CDK2, CDK1, cyclin D1, matrix metalloproteinase-9 (MMP9), and Bcl-xL. RESULTS: AZD1080 exposure suppressed ovarian cancer cell proliferation, invasion, migration, and lamellipodia formation, and induced G(1) arrest, which was concentration dependent. AZD1080 also significantly downregulated GSK-3β, CDK2, CDK1, cyclin D1, MMP9, and Bcl-xL expression at both mRNA and protein levels. CONCLUSION: Taken together, our results demonstrate that the GSK-3β inhibitor AZD1080 suppresses ovarian cancer development and therefore may indicate a new direction for ovarian cancer treatment.
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spelling pubmed-48078992016-04-05 Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer Chen, Shuo Sun, Kai-Xuan Feng, Miao-Xiao Sang, Xiu-Bo Liu, Bo-Liang Zhao, Yang Drug Des Devel Ther Original Research BACKGROUND: Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase that plays an important role in cancer tumorigenesis and progression. We investigated the role of the GSK-3β inhibitor AZD1080 in ovarian cancer cell lines. METHODS: A2780 and OVCAR3 ovarian cancer cell lines were exposed to AZD1080, after which cell proliferation, cell cycle, invasion, and migration assays were performed. Phalloidin staining was used to observe lamellipodia formation. Reverse transcription polymerase chain reaction and Western blot were used to assess the respective mRNA and protein expression levels of GSK-3β, CDK2, CDK1, cyclin D1, matrix metalloproteinase-9 (MMP9), and Bcl-xL. RESULTS: AZD1080 exposure suppressed ovarian cancer cell proliferation, invasion, migration, and lamellipodia formation, and induced G(1) arrest, which was concentration dependent. AZD1080 also significantly downregulated GSK-3β, CDK2, CDK1, cyclin D1, MMP9, and Bcl-xL expression at both mRNA and protein levels. CONCLUSION: Taken together, our results demonstrate that the GSK-3β inhibitor AZD1080 suppresses ovarian cancer development and therefore may indicate a new direction for ovarian cancer treatment. Dove Medical Press 2016-03-18 /pmc/articles/PMC4807899/ /pubmed/27051274 http://dx.doi.org/10.2147/DDDT.S102506 Text en © 2016 Chen et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Chen, Shuo
Sun, Kai-Xuan
Feng, Miao-Xiao
Sang, Xiu-Bo
Liu, Bo-Liang
Zhao, Yang
Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer
title Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer
title_full Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer
title_fullStr Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer
title_full_unstemmed Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer
title_short Role of glycogen synthase kinase-3β inhibitor AZD1080 in ovarian cancer
title_sort role of glycogen synthase kinase-3β inhibitor azd1080 in ovarian cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807899/
https://www.ncbi.nlm.nih.gov/pubmed/27051274
http://dx.doi.org/10.2147/DDDT.S102506
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