Inhibitory action of pristimerin on hypoxia‑mediated metastasis involves stem cell characteristics and EMT in PC-3 prostate cancer cells

Zuo,Jianwei; Guo,Yuanqing; Peng,Xinsheng; Tang,Yubo; Zhang,Xintao; He,Peiheng; Li,Shuaihua; Wa,Qingde; Li,Jinglei; Huang,Shuai; Xu,Dongliang

doi:10.3892/or.2015.3708

Inhibitory action of pristimerin on hypoxia‑mediated metastasis involves stem cell characteristics and EMT in PC-3 prostate cancer cells

Authors:
- Jianwei Zuo
- Yuanqing Guo
- Xinsheng Peng
- Yubo Tang
- Xintao Zhang
- Peiheng He
- Shuaihua Li
- Qingde Wa
- Jinglei Li
- Shuai Huang
- Dongliang Xu
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Affiliations: Department of Orthopaedic Surgery/Orthopaedic Research Institute, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Orthopaedic Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Sports Medicine, Shenzhen Hospital of Peking University, Shenzhen, Guangdong 518036, P.R. China, Department of Radiology, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, Guangdong 510080, P.R. China
Published online on: January 7, 2015 https://doi.org/10.3892/or.2015.3708
Pages: 1388-1394

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Abstract

The aim of the present study was to investigate whether pristimerin affects the bone metastasis, stem cell characteristics and epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) PC-3 cells subjected to hypoxia. The PC-3 cells were cultured under hypoxia or normoxia for 48 h and were then treated with increasing concentrations of pristimerin from 0 to 0.8 µmol/l, under normoxia. Hypoxia‑inducible factor-1α (HIF-1α) was detected by western blotting. Proliferation was assessed with the CCK-8 assay. Transwell invasion assay was used to analyze the potency of invasion. Stem cell characteristics were detected by sphere formation, colony formation assay and western blotting, including CD44, KLF4, OCT4 and AGO2, which are stem cell characteristic-related markers. EMT was confirmed by the expression changes of EMT-related markers, including N-cadherin, fibronectin, vimentin and ZEB1, which were evaluated by western blotting. The addition of pristimerin to the medium reduced the hypoxia-induced PC-3 cell proliferation in a dose-dependent manner. Pristimerin effectively inhibited hypoxia‑induced invasion of the PCa cells in vitro. Moreover, the treatment of cells with pristimerin induced the reversal of hypoxia-induced stem cell characteristics and EMT, which was confirmed by sphere formation, colony formation assay and the expression changes of CSC- and EMT-related markers. The reversal of hypoxia‑induced stem cell characteristics and EMT in the PCa cells by low-dose pristimerin was dose‑dependent. These results showed that treatment with pristimerin may be a potential strategy for the suppression of hypoxia-induced metastasis through the reversal of hypoxia-induced stem cell characteristics and EMT in cancer cells, which justifies the potential use of pristimerin as a practical chemopreventive approach for patients with PCa.

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