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Updated: Nov 7, 2025
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Combined α-methylacyl-CoA racemase inhibition and docetaxel treatment reduce cell proliferation and decrease
Atsuhiko Yoshizawa1, Kiyoshi Takahara1, Masanobu Saruta1
1Department of Urology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Background:
Disease progression in castrate-resistant prostate cancer (PCa) is most commonly driven by the reactivation of androgen receptor (AR) signaling and involves AR splice variants including ARV7.
Materials And Methods:
We used the ARV7-positive PCa cell line, 22Rv1, to study the relationship of the PCa marker α-methylacyl-CoA racemase (AMACR), AR, and ARV7 in PCa.
Results:
Docetaxel addition but not AMACR inhibition decreased the proliferation of 22Rv1 cells. The combination of AMACR inhibition and docetaxel treatment resulted in a maximum reduction of cell proliferation. The Western blotting analysis revealed that both AR and ARV7 expression were significantly decreased with the use of charcoal-stripped serum following AMACR inhibition and docetaxel treatment. AMACR inhibition and docetaxel treatment in the charcoal-stripped serum condition reduced the proliferation of 22Rv1, possibly via the downregulation of the heat shock protein 27.
Conclusion:
Using cell proliferation and Western blot analysis, we demonstrated that AMACR inhibition and docetaxel treatment, under androgen deprivation conditions, significantly reduced the proliferation of ARV7 positive cancer cells and decreased the levels of AR and ARV7 expression, possibly via downregulation of heat shock protein 27.
Insights
Combining AMACR inhibition with docetaxel significantly reduces proliferation in androgen receptor splice variant 7 (ARV7)-positive prostate cancer cells. This treatment also decreases AR and ARV7 expression, potentially through heat shock protein 27 downregulation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Castrate-resistant prostate cancer (PCa) progression is often driven by androgen receptor (AR) signaling reactivation.
- Androgen receptor splice variants, such as ARV7, play a crucial role in PCa disease progression.
Purpose of the Study:
- To investigate the relationship between the PCa marker AMACR, AR, and ARV7 in PCa.
- To evaluate the efficacy of AMACR inhibition combined with docetaxel in ARV7-positive prostate cancer cells.
Main Methods:
- Utilized the ARV7-positive PCa cell line, 22Rv1.
- Employed cell proliferation assays and Western blotting analysis.
- Investigated the effects of AMACR inhibition, docetaxel treatment, and androgen deprivation (charcoal-stripped serum).
Main Results:
- Docetaxel treatment, but not AMACR inhibition alone, decreased 22Rv1 cell proliferation.
- The combination of AMACR inhibition and docetaxel yielded the maximum reduction in cell proliferation.
- Both AR and ARV7 expression were significantly decreased following combined treatment under androgen deprivation, possibly via heat shock protein 27 (HSPB1) downregulation.
Conclusions:
- AMACR inhibition and docetaxel treatment, under androgen deprivation, significantly reduce proliferation in ARV7-positive prostate cancer cells.
- This combination therapy decreases AR and ARV7 expression levels.
- The observed effects may be mediated by the downregulation of heat shock protein 27.
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