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Published in: International Urology and Nephrology 4/2018

Open Access 01-04-2018 | Urology - Original Paper

Inhibiting autophagy overcomes docetaxel resistance in castration-resistant prostate cancer cells

Authors: Quan Wang, Wei-Yang He, Yi-Zhou Zeng, Arman Hossain, Xin Gou

Published in: International Urology and Nephrology | Issue 4/2018

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Abstract

Background

This study investigates the docetaxel-resistant mechanism and explores the effect of tea polyphenols (TP) on autophagy and its related mechanism in human castration-resistant prostate cancer (CRPC) cell lines PC3 and DU145.

Methods

Immunofluorescence assay and annexin V-FITC/PI double staining flow cytometry were used to analyze the apoptosis and autophagy of PC3 and DU145 cells. The expression of autophagy-related proteins was detected by western bolt.

Results

Docetaxel could induce autophagy and apoptosis, together with the expression increase in p-JNK, p-Bcl-2 and Beclin1. The level of autophagy was remarkably decreased, but apoptosis was increased after combining with TP. In addition, the expression of p-mTOR was increased after combining with TP.

Conclusion

Docetaxel induces protective autophagy in CRPC cells by JNK pathway activation and then Bcl-2 phosphorylation and Beclin1 dissociation. TP activates mTOR pathway, which ultimately inhibits docetaxel-induced autophagy and improves therapeutic efficacy of docetaxel in CRPC cells.
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Metadata
Title
Inhibiting autophagy overcomes docetaxel resistance in castration-resistant prostate cancer cells
Authors
Quan Wang
Wei-Yang He
Yi-Zhou Zeng
Arman Hossain
Xin Gou
Publication date
01-04-2018
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 4/2018
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-018-1801-5

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