Tea polyphenols inhibit docetaxel-induced autophagy and improves therapeutic efficacy of docetaxel in castration-resistant prostate cancer cells. - GreenMedInfo Summary
Inhibiting autophagy overcomes docetaxel resistance in castration-resistant prostate cancer cells.
Int Urol Nephrol. 2018 Feb 19. Epub 2018 Feb 19. PMID: 29460131
Quan Wang
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.