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BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma

BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human...

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Autores principales: Wang, Limei, Wu, Xiuyin, Wang, Ruolin, Yang, Chengzhe, Li, Zhi, Wang, Cunwei, Zhang, Fenghe, Yang, Pishan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445403/
https://www.ncbi.nlm.nih.gov/pubmed/28545522
http://dx.doi.org/10.1186/s40659-017-0124-9
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author Wang, Limei
Wu, Xiuyin
Wang, Ruolin
Yang, Chengzhe
Li, Zhi
Wang, Cunwei
Zhang, Fenghe
Yang, Pishan
author_facet Wang, Limei
Wu, Xiuyin
Wang, Ruolin
Yang, Chengzhe
Li, Zhi
Wang, Cunwei
Zhang, Fenghe
Yang, Pishan
author_sort Wang, Limei
collection PubMed
description BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 μM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound-healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. RESULTS: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial–mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. CONCLUSIONS: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.
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spelling pubmed-54454032017-05-30 BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma Wang, Limei Wu, Xiuyin Wang, Ruolin Yang, Chengzhe Li, Zhi Wang, Cunwei Zhang, Fenghe Yang, Pishan Biol Res Research Article BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 μM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound-healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. RESULTS: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial–mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. CONCLUSIONS: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment. BioMed Central 2017-05-25 /pmc/articles/PMC5445403/ /pubmed/28545522 http://dx.doi.org/10.1186/s40659-017-0124-9 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Wang, Limei
Wu, Xiuyin
Wang, Ruolin
Yang, Chengzhe
Li, Zhi
Wang, Cunwei
Zhang, Fenghe
Yang, Pishan
BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_full BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_fullStr BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_full_unstemmed BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_short BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
title_sort brd4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445403/
https://www.ncbi.nlm.nih.gov/pubmed/28545522
http://dx.doi.org/10.1186/s40659-017-0124-9
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