Therapeutic potential of siRNA-mediated combined knockdown of the IAP genes (Livin, XIAP, and Survivin) on human bladder cancer T24 cells
Therapeutic potential of siRNA-mediated combined knockdown of the IAP genes (Livin, XIAP, and Survivin) on human bladder cancer T24 cells
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siRNA介导的IAP基因（Livin、XIAP和Survivin）联合敲低对人膀胱癌T24细胞的治疗潜力
DOI：
10.1093/abbs/gmp118
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发表时间：
2010-02-01
影响因子：
3.7
通讯作者：
Shi, Wei
中科院分区：
文献类型：
--
作者：
Yang, Deyong;Song, Xishuang;Shi, Wei
Livin、X连锁凋亡抑制因子（XIAP）和存活素是三种众所周知的凋亡抑制因子，几乎仅在癌细胞中过表达，并且被认为是癌症治疗的有效靶点。在本研究中，我们发现Livin，XIAP和Survivin在膀胱癌细胞中同时表达。我们推测Livin、XIAP和Survivin可能对细胞生长和凋亡具有协同作用。我们的研究结果证实，这三个基因的联合敲除可以协同抑制高级别膀胱癌T24细胞的增殖和转化能力，并提高细胞对化疗的凋亡敏感性。此外，Livin、XIAP和Survivin的组合敲除可显著增加活性半胱天冬酶-3、活性半胱天冬酶-7、活性半胱天冬酶-9和细胞溶质Smac的丰度。我们的研究结果表明，联合沉默Livin，XIAP和Survivin可能是一种有效的多靶点基因治疗膀胱癌。
Livin, X-linked inhibitor of apoptosis (XIAP), and Survivin are three well-known inhibitors of apoptosis almost exclusively over-expressed in cancer cells and are considered potent targets for cancer treatment. In the present study, we found that Livin, XIAP, and Survivin were simultaneously expressed in bladder cancer cells. We speculated that Livin, XIAP, and Survivin might have synergistic effects on cell growth and apoptosis. Our results confirmed that combined knockdown of all these three genes can synergistically inhibit the proliferation and transformation ability of high-grade bladder cancer T24 cells and promote the cell apoptotic sensitivity to chemotherapy. Furthermore, combined knockdown of Livin, XIAP, and Survivin can markedly increase the abundance of active caspase-3, active caspase-7, active caspase-9, and cytosolic Smac. Our findings imply that combined silencing of Livin, XIAP, and Survivin may be a potent multi-targeted gene therapy for bladder cancer.