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

  • 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
  • View Affiliations

  • Published online on: May 4, 2017     https://doi.org/10.3892/or.2017.5623
  • Pages: 3651-3659
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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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June-2017
Volume 37 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Liu L, Lou N, Li X, Xu G, Ruan H, Xiao W, Qiu B, Bao L, Yuan C, Huang X, Huang X, et al: Calpain and AR-V7: Two potential therapeutic targets to overcome acquired docetaxel resistance in castration-resistant prostate cancer cells. Oncol Rep 37: 3651-3659, 2017
APA
Liu, L., Lou, N., Li, X., Xu, G., Ruan, H., Xiao, W. ... Zhang, X. (2017). Calpain and AR-V7: Two potential therapeutic targets to overcome acquired docetaxel resistance in castration-resistant prostate cancer cells. Oncology Reports, 37, 3651-3659. https://doi.org/10.3892/or.2017.5623
MLA
Liu, L., Lou, N., Li, X., Xu, G., Ruan, H., Xiao, W., Qiu, B., Bao, L., Yuan, C., Huang, X., Wang, K., Cao, Q., Chen, K., Yang, H., Zhang, X."Calpain and AR-V7: Two potential therapeutic targets to overcome acquired docetaxel resistance in castration-resistant prostate cancer cells". Oncology Reports 37.6 (2017): 3651-3659.
Chicago
Liu, L., Lou, N., Li, X., Xu, G., Ruan, H., Xiao, W., Qiu, B., Bao, L., Yuan, C., Huang, X., Wang, K., Cao, Q., Chen, K., Yang, H., Zhang, X."Calpain and AR-V7: Two potential therapeutic targets to overcome acquired docetaxel resistance in castration-resistant prostate cancer cells". Oncology Reports 37, no. 6 (2017): 3651-3659. https://doi.org/10.3892/or.2017.5623