BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma
Abstract 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:...
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Sociedad de Biología de Chile
2017
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oai:scielo:S0716-976020170001002132017-07-07BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinomaWang,LimeiWu,XiuyinWang,RuolinYang,ChengzheLi,ZhiWang,CunweiZhang,FengheYang,Pishan Salivary adenoid cystic carcinoma BRD4 inhibition Proliferation Migration Epithelial-mesenchymal transition Abstract 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.50 20172017-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100213en10.1186/s40659-017-0124-9 |
institution |
Scielo Chile |
collection |
Scielo Chile |
language |
English |
topic |
Salivary adenoid cystic carcinoma BRD4 inhibition Proliferation Migration Epithelial-mesenchymal transition |
spellingShingle |
Salivary adenoid cystic carcinoma BRD4 inhibition Proliferation Migration Epithelial-mesenchymal transition 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 |
description |
Abstract 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. |
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 |
title |
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_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_sort |
brd4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma |
publisher |
Sociedad de Biología de Chile |
publishDate |
2017 |
url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100213 |
work_keys_str_mv |
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_version_ |
1718441561474203648 |