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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner

Fei Wu1, Yun Lin2, Peng Cui3

  • 1Department of Urology, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan, 250014, People's Republic of China. urowufei@aliyun.com.

Cancer Chemotherapy and Pharmacology
|April 2, 2018
PubMed
Abstract

Insights

Cell division cycle 20 homolog (Cdc20) overexpression drives docetaxel resistance in castration-resistant prostate cancer (CRPC) by downregulating Bim. Targeting Cdc20 restores docetaxel sensitivity in CRPC cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Advanced castration-resistant prostate cancer (CRPC) lacks effective treatments.
  • Cdc20 overexpression correlates with poor prognosis in CRPC patients.
  • The mechanism of Cdc20 in docetaxel resistance is not fully understood.

Purpose of the Study:

  • To investigate the role of Cdc20 in docetaxel resistance in CRPC.
  • To elucidate the mechanism by which Cdc20 contributes to docetaxel resistance.
  • To explore Cdc20 as a therapeutic target for overcoming docetaxel resistance in CRPC.

Main Methods:

  • Confirmed Cdc20 transcription in CRPC cell lines (LNCaP, PC3, DU145).
  • Generated docetaxel-resistant (DR) cell lines and analyzed Cdc20 and Bim protein levels.
  • Utilized stable cell lines with Cdc20 or Bim deprivation and a Cdc20 inhibitor.

Main Results:

  • Cdc20 was overexpressed in DR CRPC cell lines.
  • DR cells exhibited higher Cdc20 and lower Bim protein levels compared to wild-type.
  • Cdc20 inhibition resensitized DR cells to docetaxel treatment.

Conclusions:

  • Cdc20 overexpression promotes docetaxel resistance in CRPC via a Bim-dependent pathway.
  • Targeting Cdc20 represents a potential therapeutic strategy for docetaxel-resistant CRPC.
Keywords:
BimCdc20DocetaxelProstate cancer

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