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Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial-Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α
被引:37
|作者:
Qian, Jiang
[1
]
Shen, Sheliang
[2
]
Chen, Wei
[3
]
Chen, Nianping
[4
]
机构:
[1] Zhejiang Hosp, Dept Anesthesiol, Hangzhou 310014, Zhejiang, Peoples R China
[2] Zhejiang Prov Peoples Hosp, Dept Anesthesiol, Hangzhou 310013, Zhejiang, Peoples R China
[3] Univ Chicago, Inst Mol Engn, Chicago, IL 60637 USA
[4] Zhejiang Univ, Shaoxing Hosp, Shaoxing Peoples Hosp, Dept Anesthesiol, Shaoxing 312000, Zhejiang, Peoples R China
关键词:
SUPPRESSES PROLIFERATION;
CEREBRAL-ISCHEMIA;
DOWN-REGULATION;
STEM-CELLS;
INVASION;
HIF-1-ALPHA;
APOPTOSIS;
GROWTH;
PLASTICITY;
ERA;
D O I:
10.1155/2018/4174232
中图分类号:
Q81 [生物工程学(生物技术)];
Q93 [微生物学];
学科分类号:
071005 ;
0836 ;
090102 ;
100705 ;
摘要:
Prostate cancer is the second most frequently diagnosed cancer worldwide. Hypoxia-induced epithelial-mesenchymal transition (EMT), driven by hypoxia-inducible factor 1 alpha (HIF-1 alpha), 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-1 alpha, 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-1 alpha expression, but also reversed hypoxia-induced EMT by suppressing HIF-1 alpha. Furthermore, small interfering RNA-mediated silencing of HIF-1 alpha 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-1 alpha suppression.
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页数:9
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