Up-regulation of p21WAF1/Cip1 by saRNA induces G1-phase arrest and apoptosis in T24 human bladder cancer cells
Up-regulation of p21WAF1/Cip1 by saRNA induces G1-phase arrest and apoptosis in T24 human bladder cancer cells
复制标题
saRNA上调p21WAF1/Cip1诱导T24人膀胱癌细胞G1期阻滞和细胞凋亡
DOI：
10.1016/j.canlet.2008.02.014
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发表时间：
2008-07-08
期刊：
影响因子：
9.7
通讯作者：
Xie, Li-Ping
中科院分区：
文献类型：
--
作者：
Yang, Kai;Zheng, Xiang-Yi;Xie, Li-Ping
最近的研究报道，化学合成的与靶基因启动子互补的小双链RNA可以激活不同癌细胞系中的基因表达。这种dsRNA被称为小激活RNA的saRNA。本研究旨在评估靶向p21启动子的小激活RNA诱导p21（WAF 1/Cip 1）（p21）治疗膀胱癌的潜力。使用T24人膀胱癌细胞，我们发现p21 saRNA引起细胞增殖和活力的剂量和时间依赖性抑制，这与诱导的G1期细胞周期阻滞和凋亡有关。降低的抗凋亡蛋白Bcl-xL和半胱天冬酶-3和PARP的活化也支持治疗的功效。这些数据表明，通过saRNA上调p21可能是治疗人膀胱癌和其他类型癌症的有效方法。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.