Liu Tie-gang, Yin James Q, Shang Bo-yang, Min Zhang, He Hong-wei, Jiang Jian-ming, Chen Fang, Zhen Yong-su, Shao Rong-guang
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Cancer Gene Ther. 2004 Nov;11(11):748-56. doi: 10.1038/sj.cgt.7700753.
RNA interference technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Here our results showed that hdm2-siRNA silenced its target mRNA specifically and effectively in human breast cancer cells, reduced tumor cell proliferation and induced apoptotic cell death. Other molecular features modified by hdm2-siRNA included decreased Bcl-2, NF-kappaB, survivin, Ras and Raf levels, elevated p53, p21, BRCA1, Bax, and caspase levels as well as altered expression of other genes. hdm2-siRNA also caused cell cycle arrest at G1 phases with reduction in cyclin and Cdk proteins. In addition, hdm2-siRNA displayed in vivo antitumor activity and increased therapeutic effectiveness of mitomycin in MCF-7 xenografts. Thus, hdm2-siRNA may be a promising gene-specific drug for the treatment of human breast cancer and other tumors.
RNA干扰技术是在哺乳动物细胞中沉默内源性或外源性基因的强大工具。我们的结果表明，hdm2-siRNA在人乳腺癌细胞中能特异性且有效地沉默其靶mRNA，减少肿瘤细胞增殖并诱导凋亡性细胞死亡。hdm2-siRNA改变的其他分子特征包括Bcl-2、NF-κB、生存素、Ras和Raf水平降低，p53、p21、BRCA1、Bax和半胱天冬酶水平升高以及其他基因表达改变。hdm2-siRNA还导致细胞周期停滞在G1期，同时细胞周期蛋白和细胞周期蛋白依赖性激酶蛋白减少。此外，hdm2-siRNA在体内显示出抗肿瘤活性，并增强了丝裂霉素对MCF-7异种移植瘤的治疗效果。因此，hdm2-siRNA可能是一种有前景的用于治疗人类乳腺癌和其他肿瘤的基因特异性药物。
