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

目的：研究Aurora-A基因表达对膀胱癌细胞生长和化疗敏感性的抑制作用。方法：采用真实的时间RT-PCR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KoTCC 1细胞，其中引入了含有靶向Aurora-A的短发夹RNA（shRNA）的表达载体（KoTCC 1/Aurora）。将KoTCC 1/Aurora中的生长和对几种治疗剂的敏感性与单独转染对照载体的KoTCC 1（KoTCC 1/Co）中的生长和对几种治疗剂的敏感性进行比较。KoTCC 1/Aurora的Aurora-A mRNA和蛋白表达水平均为KoTCC 1/Co的20%，其体外生长明显不如KoTCC 1/Co，多西紫杉醇和舒尼替尼的50%抑制浓度均较KoTCC 1/Co降低。使用shRNA抑制Aurora-A可能是一种有用的膀胱癌治疗策略，通过生长抑制以及增强化学敏感性。

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.