Inhibition of tumor growth and sensitization to chemotherapy by RNA interference targeting Aurora-A in the human bladder cancer KoTCC1 model.

• Project/Area Number: 21791502
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Kobe University
• Principal Investigator: SAKAI Iori Kobe University, 医学部附属病院, 医員 (20533772)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: Aurora-A / siRNA / 膀胱癌 / 抗がん剤感受性 / shRNA / Aurora kinase

Research Abstract

OBJECTIVES : To investigate the inhibitory effects of Aurora-A expression in bladder cancer cells on their growth and chemosensitivity. METHODS : Aurora-A expression in several human bladder cancer cell lines were evaluated by real time RT-PCR. We then established KoTCC1 cells in which the expression vector containing short-hairpin RNA (shRNA) targeting Aurora-A was introduced (KoTCC1/Aurora). The growth and the sensitivity to several therapeutic agents in KoTCC1/Aurora were compared with those in KoTCC1 transfected with control vector alone (KoTCC1/Co). Expression levels of both Aurora-A mRNA and protein in KoTCC1/Aurora were 20% of those in KoTCC1/Co. In vitro growth of KoTCC1/ Aurora was significantly worse than that of KoTCC1/Co. The 50% inhibitory concentration of docetaxel and sunitninb in KoTCC1/Aurora decreased compared with that in KoTCC1/Co. CONCLUSIONS : The suppression of Aurora-A using shRNA could be a useful therapeutic strategy against bladder cancer, through growth inhibition as well as enhanced chemosensitivity.

Research Products

• [Journal Article] Inhibition of tumor growth and sensitization to chemotherapy by RNA interference targeting interleukin-6 in the androgen-independent human prostate cancer PC3 model. (2011)
  • Author(s): Sakai I, Miyake H, Terakawa T, Fujisawa M.
  • Journal Title: Cancer Sci. 102(4) Pages: 769-75
  • NAID: 10029292277
• [Journal Article] Assessment of long-term quality of life in patients with orthotopic neobladder followed for more than 5 years. (2010)
  • Author(s): Takenaka A, Hara I, Soga H, Sakai I, Terakawa T, Muramaki M, Miyake H, Tanaka K, Fujisawa M.
  • Journal Title: Int Urol Nephrol.
• [Journal Article] Expression profile of E-cadherin and N-cadherin in non-muscle-invasive bladder cancer as a novel predictor of intravesical recurrence following transurethral resection. (2010)
  • Author(s): Muramaki M, Miyake H, Terakawa T, Kumano M, Sakai I, Fujisawa M.
  • Journal Title: Urol Oncol.
• [Journal Article] Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ. (2006)
  • Author(s): Sakai I, Miyake H, Harada K, Hara I, Inoue TA, Fujisawa M.
  • Journal Title: Int J Urol. 13(11) Pages: 1389-92
  • NAID: 10019379713
• [Journal Article] Inhibition of tumor growth and sensitization to chemotherapy by RNA interference targeting Aurora-A in the human bladder cancer KoTCC1 model.
  • Author(s): Iori Sakai
  • Journal Title: BJU international Volume: (In Press)
  • Peer Reviewed