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Updated: Jan 20, 2026

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

Published on: September 8, 2017

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TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer

Yohei Sekino1, Xiangrui Han2, Takafumi Kawaguchi2

  • 1Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. akikosekino@gmail.com.

International Journal of Molecular Sciences
|August 16, 2019
PubMed

Insights

Tubulin beta 3 (TUBB3) overexpression drives docetaxel and cabazitaxel resistance in prostate cancer. Reducing TUBB3 re-sensitizes cells to these treatments, suggesting combination therapies for improved outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Prostate cancer (PCa) often develops resistance to chemotherapy, including docetaxel (DTX) and cabazitaxel (CBZ).
  • Overexpression of Tubulin beta 3 (TUBB3) has been implicated in DTX resistance in PCa.
  • The precise role of TUBB3 in resistance to both DTX and CBZ, and the cross-resistance phenomenon, requires further elucidation.

Purpose of the Study:

  • To investigate the role of TUBB3 in DTX and CBZ resistance in PCa.
  • To determine if TUBB3 mediates cross-resistance between DTX and CBZ.
  • To explore the interplay between TUBB3, PTEN, and the phosphoinositide 3-kinases (PI3K) pathway in chemoresistance.

Main Methods:

  • TUBB3 knockdown was performed to assess its impact on DTX and CBZ resistance.
  • Interactions between TUBB3 and PTEN were examined.
  • The effect of a PI3K inhibitor (LY294002) on TUBB3 expression and chemoresistance was investigated.

Main Results:

  • TUBB3 expression was elevated in both DTX-resistant and CBZ-resistant PCa cells.
  • TUBB3 knockdown restored sensitivity to DTX and CBZ, and also re-sensitized cells to the alternative drug, indicating TUBB3 mediates cross-resistance.
  • Knockdown of TUBB3 increased PTEN expression, while PTEN knockout increased TUBB3 expression. LY294002 inhibited TUBB3 expression and re-sensitized resistant cells to both DTX and CBZ.

Conclusions:

  • TUBB3 is a key mediator of both DTX and CBZ resistance in prostate cancer.
  • The PI3K pathway, influenced by PTEN, plays a role in regulating TUBB3 expression and chemoresistance.
  • Combining LY294002 with DTX or CBZ presents a promising therapeutic strategy for overcoming chemoresistance in PCa.
Keywords:
LY294002PTENTUBB3cabazitaxelcross-resistancedocetaxelprostate cancer

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