Zou Lin, Zhang Penghui, Luo Chunli, Tu Zhiguang
Faculty of Laboratory Medicine in Chongqing, University of Medical Sciences, China.
Cancer Chemother Pharmacol. 2006 Feb;57(3):328-34. doi: 10.1007/s00280-005-0056-x. Epub 2005 Jul 19.
RNA interference (RNAi) has demonstrated profound prospect in human gene research. hTERT, the rate-limiting component of telomerase activity, is highly expressed in bladder cancer cells. Here, we investigated the anti-proliferation effects of small hairpin interfering RNA (shRNA)-targeted hTERT gene on bladder cancer in vitro and in vivo. The results showed that ph2-shRNA, the most-effective vector carrying shRNA-targeted hTERT, could significantly inhibit the cell proliferation by down-regulating hTERT expression, decreasing telomerase activity, decreasing cell number of S phase, increasing the cell number of G0/G1 phase in T24 cells and xenograft tumor tissues, and attenuate the tumor growth of xenograft mice model compared with controls. Our results demonstrate that hTERT-directed shRNAs are potent inhibitors of bladder cancer.
RNA干扰(RNAi)在人类基因研究中已展现出深远前景。端粒酶活性的限速成分人端粒酶逆转录酶(hTERT)在膀胱癌细胞中高表达。在此,我们研究了靶向hTERT基因的小发夹干扰RNA(shRNA)对膀胱癌的体内外抗增殖作用。结果显示,ph2-shRNA是携带靶向hTERT的shRNA的最有效载体,与对照组相比,它可通过下调hTERT表达、降低端粒酶活性、减少T24细胞和异种移植肿瘤组织中S期细胞数量、增加G0/G1期细胞数量,显著抑制细胞增殖,并减缓异种移植小鼠模型的肿瘤生长。我们的结果表明,靶向hTERT的shRNAs是膀胱癌的有效抑制剂。