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Updated: Mar 3, 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

14.1K

Targeting AXL overcomes resistance to docetaxel therapy in advanced prostate cancer

Jian-Zhong Lin1, Zeng-Jun Wang2, Wei De3

  • 1Department of Urology, BenQ Medical Center, Nanjing Medical University, Nanjing, China.

Oncotarget
|April 30, 2017
PubMed

Insights

AXL receptor tyrosine kinase (AXL) overexpression drives docetaxel resistance in prostate cancer. Inhibiting AXL with docetaxel may improve treatment response and overcome resistance in advanced prostate cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Docetaxel resistance is a significant challenge in advanced prostate cancer treatment.
  • AXL receptor tyrosine kinase (AXL) overexpression is linked to chemotherapy resistance, but its specific role in docetaxel resistance in prostate cancer remains unclear.

Purpose of the Study:

  • To investigate the role of AXL in docetaxel resistance in prostate cancer.
  • To evaluate the therapeutic potential of AXL inhibition in combination with docetaxel.

Main Methods:

  • Utilized docetaxel-resistant prostate cancer cell lines (PC3-DR, DU145-DR) and parental cell lines (PC3, DU145).
  • Assessed AXL expression and activation, and the effects of AXL inhibition (genetic/pharmacologic) on cell proliferation, migration, invasion, and tumor growth.
  • Investigated the impact of AXL inhibition on epithelial-mesenchymal transition (EMT) and ATP-binding cassette B1 (ABCB1) expression.

Main Results:

  • AXL was overexpressed and activated in docetaxel-resistant prostate cancer cells, independent of Gas6.
  • Forced AXL overexpression induced docetaxel resistance in sensitive cell lines.
  • AXL inhibition suppressed proliferation, migration, invasion, and tumor growth, with synergistic effects when combined with docetaxel.
  • AXL inhibition reversed EMT phenotype and decreased ABCB1 expression.

Conclusions:

  • AXL is a key mediator of docetaxel resistance in prostate cancer.
  • Targeting AXL in combination with docetaxel offers a promising strategy to enhance treatment efficacy and overcome resistance in advanced prostate cancer.
Keywords:
ATP-binding cassette B1 (ABCB1)AXLdocetaxel resistanceepithelial-mesenchymal transition (EMT)prostate cancer

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