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

目的：探讨Aurora-A在膀胱癌细胞中的表达对其生长和化疗敏感性的抑制作用。方法：采用实时RT-PCR技术检测Aurora-A在几种人膀胱癌细胞系中的表达。然后，我们建立了KoTCC1细胞，其中引入了靶向Aurora- a的短发夹RNA （short-hairpin RNA, shRNA）表达载体（KoTCC1/Aurora）。比较KoTCC1/Aurora与单独转染对照载体（KoTCC1/Co）的KoTCC1的生长情况和对几种治疗药物的敏感性。KoTCC1/Aurora中Aurora- a mRNA和蛋白的表达量均为KoTCC1/Co的20%。KoTCC1/ Aurora的体外生长明显差于KoTCC1/Co。多西他赛和舒尼尼在KoTCC1/Aurora中的50%抑制浓度较KoTCC1/Co降低。结论：利用shRNA抑制Aurora-A可能是一种有效的治疗策略，可通过抑制生长和增强化疗敏感性来治疗膀胱癌。

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.