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Am J Transl Res 2013;5(3):359-367
Original Article
AURKA suppression induces DU145 apoptosis and sensitizes DU145 to
docetaxel treatment
Wei He, Min-Guang Zhang, Xiao-Jing Wang, Shan Zhong, Yuan Shao, Yu Zhu, Zhou-Jun Shen
Department of Urology, Ruijin hospital, Shanghai Jiaotong University, school of medicine, Shanghai, China
Received March 7, 2013; Accepted March 22, 2013; Epub April 19, 2013; Published April 30, 2013
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. (AJTR1303003).
Keywords: Prostate cancer, AURKA, p53, docetaxel, castration-resistant prostate cancer, aurora kinases
Address correspondence to: Dr. Zhou-Jun Shen, Department of Urology, Ruijin Hospital, Shanghai Jiaotong
University, School of Medicine, Shanghai, China. Phone: 86-13917138608; E-mail: shenzhoujun6@163.com
Original Article
AURKA suppression induces DU145 apoptosis and sensitizes DU145 to
docetaxel treatment
Wei He, Min-Guang Zhang, Xiao-Jing Wang, Shan Zhong, Yuan Shao, Yu Zhu, Zhou-Jun Shen
Department of Urology, Ruijin hospital, Shanghai Jiaotong University, school of medicine, Shanghai, China
Received March 7, 2013; Accepted March 22, 2013; Epub April 19, 2013; Published April 30, 2013
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. (AJTR1303003).
Keywords: Prostate cancer, AURKA, p53, docetaxel, castration-resistant prostate cancer, aurora kinases
Address correspondence to: Dr. Zhou-Jun Shen, Department of Urology, Ruijin Hospital, Shanghai Jiaotong
University, School of Medicine, Shanghai, China. Phone: 86-13917138608; E-mail: shenzhoujun6@163.com
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