IKK inhibitor suppresses epithelial-mesenchymal transition and induces cell death in prostate cancer

Ping,Hao; Yang,Feiya; Wang,Mingshuai; Niu,Yinong; Xing,Nianzeng

doi:10.3892/or.2016.4915

IKK inhibitor suppresses epithelial-mesenchymal transition and induces cell death in prostate cancer

Authors:
- Hao Ping
- Feiya Yang
- Mingshuai Wang
- Yinong Niu
- Nianzeng Xing
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Affiliations: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China
Published online on: July 7, 2016 https://doi.org/10.3892/or.2016.4915
Pages: 1658-1664

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Abstract

IκB kinase (IKK)/nuclear factor κB (NF-κB) pathway activation is a key event in the acquisition of invasive and metastatic capacities in prostate cancer. A potent small-molecule compound, BMS-345541, was identified as a highly selective IKKα and IKKβ inhibitor to inhibit kinase activity. This study explored the effect of IKK inhibitor on epithelial-mesenchymal transition (EMT), apoptosis and metastasis in prostate cancer. Here, we demonstrate the role of IKK inhibitor reducing proliferation and inducing apoptosis in PC-3 cells. Furthermore, BMS345541 inhibited IκBα phosphorylation and nuclear level of NF-κB/p65 in PC-3 cells. We also observed downregulation of the N-cadherin, Snail, Slug and Twist protein in a dose-dependent manner. BMS‑345541 induced upregulation of the epithelial marker E-cadherin and phosphorylated NDRG1 at protein level. Moreover, BMS‑345541 reduced invasion and metastasis of PC-3 cells in vitro. In conclusion, IKK has a key role in both EMT and apoptosis of prostate cancer. IKK inhibitor can reverse EMT and induce cell death in PCa cells. IKK was identified as a potential target structure for future therapeutic intervention in PCa.

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