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2017 ; 50
(1
): 19
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BRD4 inhibition suppresses cell growth, migration and invasion of salivary
adenoid cystic carcinoma
#MMPMID28545522
Wang L
; Wu X
; Wang R
; Yang C
; Li Z
; Wang C
; Zhang F
; Yang P
Biol Res
2017[May]; 50
(1
): 19
PMID28545522
show ga
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 ?M. 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.