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.
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Authors | Lei Liu, Ning Lou, Xiang Li, Guanghua Xu, Hailong Ruan, Wen Xiao, Bin Qiu, Lin Bao, Changfei Yuan, Xinmian Huang, Keshan Wang, Qi Cao, Ke Chen, Hongmei Yang, Xiaoping Zhang |
Journal | Oncology reports
(Oncol Rep)
Vol. 37
Issue 6
Pg. 3651-3659
(Jun 2017)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 28498452
(Publication Type: Journal Article)
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Chemical References |
- Androgens
- Protein Isoforms
- Quinazolines
- Receptors, Androgen
- Taxoids
- importazole
- Docetaxel
- Calpain
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Topics |
- Androgens
(genetics, metabolism)
- Calpain
(genetics)
- Cell Line, Tumor
- Docetaxel
- Drug Resistance, Neoplasm
(genetics)
- Gene Expression Regulation, Neoplastic
(genetics)
- Humans
- Male
- Prostatic Neoplasms, Castration-Resistant
(drug therapy, genetics, pathology)
- Protein Isoforms
(genetics)
- Quinazolines
(administration & dosage)
- Receptors, Androgen
(genetics)
- Signal Transduction
(drug effects)
- Taxoids
(administration & dosage)
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