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Biomed Res Int. 2018 Jan 11;2018:4174232. doi: 10.1155/2018/4174232. eCollection 2018.

Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial-Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α.

Author information

1
Department of Anesthesiology, Zhejiang Hospital, Hangzhou, Zhejiang 310014, China.
2
Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310013, China.
3
Institute of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
4
Department of Anesthesiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, China.

Abstract

Prostate cancer is the second most frequently diagnosed cancer worldwide. Hypoxia-induced epithelial-mesenchymal transition (EMT), driven by hypoxia-inducible factor 1α (HIF-1α), is involved in cancer progression and metastasis. The present study was designed to explore the role of propofol in hypoxia-induced resistance of prostate cancer cells to docetaxel. We used the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assay to measure cell viability and cell proliferation, respectively, in prostate cancer cell lines. Then, we detected HIF-1α, E-cadherin, and vimentin expression using western blotting. Propofol reversed the hypoxia-induced docetaxel resistance in the prostate cancer cell lines. Propofol not only decreased hypoxia-induced HIF-1α expression, but also reversed hypoxia-induced EMT by suppressing HIF-1α. Furthermore, small interfering RNA-mediated silencing of HIF-1α reversed the hypoxia-induced docetaxel resistance, although there was little change in docetaxel sensitivity between the hypoxia group and propofol group. The induction of hypoxia did not affect E-cadherin and vimentin expression, and under the siRNA knockdown conditions, the effects of propofol were obviated. These data support a role for propofol in regulating EMT in prostate cancer cells. Taken together, our findings demonstrate that propofol plays an important role in hypoxia-induced docetaxel sensitivity and EMT in prostate cancer cells and that it is a potential drug for overcoming drug resistance in prostate cancer cells via HIF-1α suppression.

PMID:
29568752
PMCID:
PMC5820676
DOI:
10.1155/2018/4174232
[Indexed for MEDLINE]
Free PMC Article

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