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Oncol Rep. 2017 Jun;37(6):3651-3659. doi: 10.3892/or.2017.5623. Epub 2017 May 4.

Calpain and AR-V7: Two potential therapeutic targets to overcome acquired docetaxel resistance in castration-resistant prostate cancer cells.

Author information

1
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
2
Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

Abstract

Docetaxel-based chemotherapy has been widely used as the first-line treatment for castration-resistant prostate cancer (CRPC) patients. However, the mechanisms of docetaxel-resistance remain unclear. In the present study with the establishment of 2 in vitro models of docetaxel-resistant CRPC cell sublines, we firstly reported that activation of calpain may play a promotional role in the resistance of docetaxel in prostate cancer, meanwhile using the calpain inhibitor combined with docetaxel improved the efficiency of docetaxel in docetaxel-resistant cell sublines. Moreover, we also found that the expression of androgen-independent constitutively and transcriptionally active androgen receptor splice variant-7 (AR-V7) remained high in the docetaxel-resistant CRPC cell subline Rv1-DR, and that it may be involved in acquired docetaxel-resistance of CRPC. However, a novel importin-β inhibitor (importazole) was only capable of slightly decreasing the transcriptional activity of the AR signaling pathway via blocking nuclear import of AR-FL and various non-specific AR-Vs, instead of AR-V7. These findings suggest that calpain and AR-V7 may serve as important biomarkers in the treatment of CRPC, and targeting calpain and AR-V7 may provide a new approach in overcoming docetaxel-resistance.

PMID:
28498452
DOI:
10.3892/or.2017.5623
[Indexed for MEDLINE]

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