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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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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. |
format | Online Article Text |
id | pubmed-5445403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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