Related Experiment Video

Updated: Apr 12, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

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Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel Resistance in Advanced Prostate Cancer

Yezi Zhu1, Chengfei Liu2, Cameron Armstrong2

  • 1Department of Urology, University of California at Davis, Sacramento, California. Graduate Program in Pharmacology and Toxicology, University of California at Davis, Sacramento, California.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 22, 2015
PubMed
Abstract

Insights

Antiandrogens bicalutamide and enzalutamide inhibit ABCB1 transporter activity, overcoming docetaxel resistance in prostate cancer cells. This finding supports new combination therapies for advanced prostate cancer, regardless of androgen receptor status.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Acquired resistance to docetaxel is a major challenge in advanced prostate cancer treatment.
  • ABCB1 (P-glycoprotein) is a key efflux pump contributing to multidrug resistance.
  • Inhibiting ABCB1 is a strategy to overcome docetaxel resistance.

Purpose of the Study:

  • To investigate if antiandrogens bicalutamide and enzalutamide can inhibit ABCB1 activity.
  • To determine if these antiandrogens can overcome docetaxel resistance in prostate cancer cells.
  • To explore the potential for combination therapy with docetaxel.

Main Methods:

  • Assessed ABCB1 efflux activity using rhodamine efflux assays.
  • Measured ABCB1 ATPase activity with Pgp-Glo assay systems.
  • Evaluated antiandrogen effects on docetaxel sensitivity via cell growth and in vivo tumor growth assays.

Main Results:

  • Bicalutamide and enzalutamide inhibited ABCB1 efflux activity (40% and 60%, respectively) and ATPase activity.
  • These antiandrogens desensitized docetaxel-resistant, androgen receptor (AR)-negative DU145 cells.
  • Combination therapy with bicalutamide and docetaxel showed significant antitumor effects in both AR-positive and AR-negative xenografts.

Conclusions:

  • Bicalutamide and enzalutamide act as novel inhibitors of ABCB1 efflux and ATPase activity.
  • These antiandrogens resensitize docetaxel-resistant prostate cancer cells to docetaxel, independent of AR status.
  • Combination therapies with bicalutamide/enzalutamide and docetaxel show promise for treating advanced prostate cancer, irrespective of AR status.

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