Downregulation of BRD4 inhibits gallbladder cancer proliferation and metastasis and induces apoptosis via PI3K/AKT pathway

Hao,Jiaqi; Yang,Ziyi; Wang,Lei; Zhang,Yijian; Shu,Yijun; Jiang,Lin; Hu,Yunping; Lv,Wenjie; Dong,Ping; Liu,Yingbin

doi:10.3892/ijo.2017.4081

Downregulation of BRD4 inhibits gallbladder cancer proliferation and metastasis and induces apoptosis via PI3K/AKT pathway

Authors:
- Jiaqi Hao
- Ziyi Yang
- Lei Wang
- Yijian Zhang
- Yijun Shu
- Lin Jiang
- Yunping Hu
- Wenjie Lv
- Ping Dong
- Yingbin Liu
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Affiliations: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China, Department of Hepatobiliary Surgery, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, P.R. China
Published online on: July 27, 2017 https://doi.org/10.3892/ijo.2017.4081
Pages: 823-831
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bromodomain containing protein 4 (BRD4) has been demonstrated to play a critical role in tumor progression. However, the expression and function of BRD4 in gallbladder cancer (GBC) are still unknown. In this study, we report that BRD4 expression level was significantly upregulated in GBC tissues and GBC cell lines. We explored the correlation between BRD4 levels and clinicopathological data of GBC patients. The high expression level of BRD4 was notably correlated with the poor prognosis of GBC patients. Knockdown of BRD4 suppressed proliferation and migration in NOZ and EH-GB1 cells. The depletion of BRD4 in GBC cell lines resulted in obvious cell apoptosis and downregulated the expression levels of Bcl-2, p-PI3K and p-AKT. In vivo, tumor volumes of nude mice were significantly decreased in BRD4 silenced group. Our data suggested that downregulation of BRD4 in GBC cells induced apoptosis by PI3K/AKT pathway. Inhibition of BRD4 expression may be a novel therapeutic strategy for patients with GBC.

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