Wang R, Lin F, Wang X, Gao P, Dong K, Zou A-M, Cheng S-Y, Wei S-H, Zhang H-Z
Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Cancer Gene Ther. 2008 Jun;15(6):402-12. doi: 10.1038/cgt.2008.16. Epub 2008 Mar 14.
Livin, a novel member of the human inhibitors of apoptosis protein (IAP) family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. To investigate its possibility as a therapeutic target for human malignancies, we established two genetically different stable tumor cell lines (LoVo and SPCA-1) and RNA interference (RNAi) technique was employed to downregulate Livin expression in two human tumor cell lines. The specific downregulation of Livin expression in tumor cell lines significantly inhibited in vitro cell proliferation and in vivo tumorigenicity. Furthermore, Livin knockdown led to cell arrest in the G(1)/G(0) phase of cell cycle, eventual apoptosis and chemosensitivity enhancement in tumor cells. All these results indicate that RNAi-mediated downregulation of Livin expression can lead to potent antitumor activity and chemosensitizing effects in human cancers.
生存素是人类凋亡抑制蛋白（IAP）家族的一个新成员，通过抑制细胞凋亡在肿瘤进展和发生过程中发挥重要作用。它在人类最常见的肿瘤中选择性表达，似乎参与肿瘤细胞对化疗药物的耐药。为了研究其作为人类恶性肿瘤治疗靶点的可能性，我们建立了两种基因不同的稳定肿瘤细胞系（LoVo和SPCA-1），并采用RNA干扰（RNAi）技术下调两种人类肿瘤细胞系中的生存素表达。肿瘤细胞系中生存素表达的特异性下调显著抑制了体外细胞增殖和体内致瘤性。此外，生存素表达降低导致细胞周期停滞于G(1)/G(0)期，最终导致肿瘤细胞凋亡并增强其化学敏感性。所有这些结果表明，RNAi介导的生存素表达下调可在人类癌症中产生强大的抗肿瘤活性和化学增敏作用。
