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Updated: May 11, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
AURKA suppression induces DU145 apoptosis and sensitizes DU145 to docetaxel treatment
Wei He1, Min-Guang Zhang, Xiao-Jing Wang
1Department of Urology, Ruijin hospital, Shanghai Jiaotong University, school of medicine Shanghai, China.
Abstract:
The palliative therapy effect by docetaxel for CRPC patients makes it urgent to improve the therapy. It was suggested that PI3K and androgen receptor-directed combination therapy may be effective for prostate cancer (PCa) patients PTEN negative. However, for those patients PTEN positive, the mechanism of anti-apoptosis survival of cancer cells is not yet well defined. Amplification of AURKA has been detected in 5% of PCa. In this work, Du145, a PTEN positive PCa cell model, was employed to investigate the role of aurora kinase a (AURKA) on cell growth. Inhibition of AURKA expression by shRNA markedly reduced prostate cancer cell viability. Furthermore, we demonstrate that AURKA inhibition induced a remarkable downregulation of AKT activity and Bax induction. Moreover, specific inhibition of the activity of AURKA, but not other aurora family members, by small molecular chemical inhibitors induced significant cell killing effects. Notably, AURKA inhibition sensitized prostate cancer cells to docetaxel treatment. Our work suggests that AURKA-directed monotherapy or combination therapy with docetaxel could be a potent treatment for PCa patients in future.
Insights
Aurora kinase A (AURKA) inhibition significantly reduces prostate cancer cell viability and sensitizes cells to docetaxel. Targeting AURKA offers a potential new therapeutic strategy for prostate cancer (PCa).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Docetaxel palliative therapy for castration-resistant prostate cancer (CRPC) necessitates improved treatment strategies.
- While PI3K and androgen receptor-directed therapies show promise for PTEN-negative prostate cancer (PCa), mechanisms of anti-apoptosis survival in PTEN-positive PCa remain unclear.
- Aurora kinase A (AURKA) amplification occurs in 5% of PCa cases, suggesting its potential role in cancer progression.
Purpose of the Study:
- To investigate the role of aurora kinase A (AURKA) in the growth of PTEN-positive prostate cancer (PCa) cells.
- To explore AURKA's impact on cell viability, apoptosis-related proteins, and sensitivity to docetaxel.
Main Methods:
- Utilized Du145, a PTEN-positive PCa cell line, as a model system.
- Employed short hairpin RNA (shRNA) to inhibit AURKA expression.
- Administered specific small molecular chemical inhibitors targeting AURKA activity.
- Assessed cell viability, AKT activity, and Bax protein levels.
Main Results:
- Inhibition of AURKA expression significantly reduced prostate cancer cell viability.
- AURKA inhibition led to decreased AKT activity and increased Bax induction, suggesting a role in apoptosis.
- Specific inhibition of AURKA, but not other aurora kinases, resulted in significant cell killing.
- AURKA inhibition enhanced the sensitivity of prostate cancer cells to docetaxel treatment.
Conclusions:
- AURKA plays a critical role in the survival and proliferation of PTEN-positive prostate cancer cells.
- AURKA-directed monotherapy presents a potential treatment avenue for PCa.
- Combination therapy involving AURKA inhibition and docetaxel may offer a potent therapeutic strategy for future PCa treatment.
