Yang Kai, Zheng Xiang-Yi, Qin Jie, Wang Yun-Bin, Bai Yu, Mao Qi-Qi, Wan Qun, Wu Zhi-Ming, Xie Li-Ping
Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou 310003, Zhejiang Province, China.
Cancer Lett. 2008 Jul 8;265(2):206-14. doi: 10.1016/j.canlet.2008.02.014. Epub 2008 Mar 20.
Very recent studies have reported that chemically synthesized small duplex RNAs complementary to the promoters of target genes can activate gene expression in different cancer cell lines. Such dsRNA have been referred to as saRNA for small activating RNA. The present study was conducted to evaluate the potential of p21(WAF1/Cip1) (p21) induction by small activating RNA targeting the p21 promoter in the treatment of bladder cancer. Using T24 human bladder cancer cells, we found that p21 saRNA caused dose- and time-dependent inhibition of cell proliferation and viability which was associated with induced G1-phase cell cycle arrest and apoptosis. The decreased anti-apoptotic protein Bcl-xL and activation of caspase-3 and PARP also supported the efficacy of the treatment. These data suggest that up-regulation of p21 by saRNA may be an effective way for treating human bladder and other types of cancers.
最近的研究报道，与靶基因启动子互补的化学合成小双链RNA可在不同癌细胞系中激活基因表达。这种双链RNA被称为小激活RNA（saRNA）。本研究旨在评估靶向p21启动子的小激活RNA诱导p21（WAF1/Cip1）（p21）表达在膀胱癌治疗中的潜力。使用T24人膀胱癌细胞，我们发现p21 saRNA导致细胞增殖和活力呈剂量和时间依赖性抑制，这与诱导G1期细胞周期停滞和凋亡有关。抗凋亡蛋白Bcl-xL的减少以及caspase-3和PARP的激活也支持了该治疗的有效性。这些数据表明，saRNA上调p21可能是治疗人类膀胱癌和其他类型癌症的有效方法。
