Shen Jianjun, Liu Jiayun, Long Yin, Miao Yinye, Su Mingquan, Zhang Qing, Han Hua, Hao Xiaoke
Department of Clinical Laboratory, Xijing Hospital, Fourth Military Medical University, Xioan 710032, China.
Acta Biochim Biophys Sin (Shanghai). 2009 Mar;41(3):223-30. doi: 10.1093/abbs/gmp005.
Survivin, a member of inhibitor of apoptosis family protein, has become an attractive therapeutic target in cancer due to its selective expression in tumor cells and its important roles for tumor cell viability. Here, we show that vector-based small interfering RNAs (siRNAs) silenced survivin expression in prostate cancer cells, resulting in significantly reduced cell proliferation and enhanced apoptosis, and increased the sensitivity of prostate cancer cells (PC-3) to the apoptosis- inducing agent, platinol. Furthermore, PC-3 cells transfected with the siRNA-expressing vector showed lower tumor formation in nude mice xenografts in vivo. These results demonstrated that inhibition of survivin expression by siRNA attenuated the malignant phenotypes of prostate cancer cells, and may provide a novel approach for gene therapy of androgen-independent prostate cancer.
生存素是凋亡抑制蛋白家族的成员之一,由于其在肿瘤细胞中的选择性表达及其对肿瘤细胞生存能力的重要作用,已成为癌症中一个有吸引力的治疗靶点。在此,我们表明基于载体的小干扰RNA(siRNA)可沉默前列腺癌细胞中的生存素表达,导致细胞增殖显著减少、凋亡增强,并增加前列腺癌细胞(PC-3)对凋亡诱导剂顺铂的敏感性。此外,用表达siRNA的载体转染的PC-3细胞在体内裸鼠异种移植中显示出较低的肿瘤形成。这些结果表明,siRNA抑制生存素表达可减弱前列腺癌细胞的恶性表型,并可能为雄激素非依赖性前列腺癌的基因治疗提供一种新方法。