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

Limei Wang,Pishan Yang,Fenghe Zhang,Cunwei Wang,Zhi Li,Chengzhe Yang,Xiuyin Wu,Ruolin Wang

doi:10.1186/s40659-017-0124-9

Abstract

BackgroundBromodomain-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).MethodsThe 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.ResultsJQ1 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.ConclusionsBRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.

Highlights

Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies
We investigated the effect of BRD4 inhibition by JQ1 on cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC) cells in vitro, so as to develop a new therapeutic target for SACC
JQ1 exhibits no adverse effects on proliferation, cell apoptosis and cell cycle of the human normal epithelial cells Firstly, we investigated the effects of JQ1 at various concentrations on proliferation, cell apoptosis and cell cycle of the human normal epithelial cells

Summary

Introduction

Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. Salivary adenoid cystic carcinoma (SACC) is a highly malignant carcinoma that most often arises from the secretory epithelial cells of salivary glands [1] and Recent studies have demonstrated that epigenetic regulators are becoming new therapeutic targets for cancer therapy [6], of which as a member of the bromodomain and extraterminal domain (BET) proteins, Wang et al Biol Res (2017) 50:19 bromodomain-containing protein 4 (BRD4) has been widely investigated. Studies of yeast and mammalian BET family proteins, including BRD4, indicate that they recognize acetylated chromatin in vivo and regulate the expression of important oncogenes, for example, c-myc and BCL-2 [13]. BRD4 plays important roles in genesis, development and metastasis of tumors

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