Reversal of docetaxel resistance in prostate cancer by Notch signaling inhibition

Acquired docetaxel (Doc) resistance in hormone-refractory prostate cancer (HRPC) remains an ongoing clinical challenge, resulting in failed chemotherapy and tumor recurrence. However, the mechanism of Doc-resistance development in prostate cancer cells is still unclear. Here, we observed a subpopulation of prostate cancer cells, in both Doc-resistant cell lines and the tumors of patients with HRPC, which show stem cell markers and greater tumorigenic potential. Those stem-like prostate cancer cells show high expression of ABCB1, which encodes multidrug resistance-related protein P-glycoprotein, leading to the Doc-resistance in prostate cancer. Moreover, we found that Notch signaling pathway activation in Doc-resistant cell lines and tumor tissues of patients with HRPC correlated with tumorigenicity and the development of Doc resistance. Here, we revealed that a combination of Doc and a Notch signaling inhibitor overcomes Doc resistance and increases the survival of mice with Doc-resistant xenografts. Therefore, targeting the Notch signaling pathway may be a promising strategy to overcome the Doc-resistant cancer in the clinic. *Shi Qiu, Linghui Deng, and Yige Bao contributed equally to the writing of this article. Correspondence to Qiang Wei, MD, Department of Urology, Institute of Urology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan 610041, People's Republic of China Tel: +86 189 806 01425; fax: +86 288 558 2944; e-mail: weiqiang163163@163.com or Correspondence to Lu Yang, MD, Department of Urology, Institute of Urology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan 610041, People's Republic of China Tel: +86 135 412 35213; fax: +86 288 558 2944; e-mail: wycleflue@163.com Received January 22, 2018 Accepted May 17, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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