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Am J Transl Res. 2013 Apr 19;5(3):359-67. Print 2013.

AURKA suppression induces DU145 apoptosis and sensitizes DU145 to docetaxel treatment.

Author information

1
Department 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.

KEYWORDS:

AURKA; Prostate cancer; aurora kinases; castration-resistant prostate cancer; docetaxel; p53

PMID:
23634246
PMCID:
PMC3633978
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