Antitumor activities of an oncolytic adenovirus equipped with a double siRNA targeting Ki67 and hTERT in renal cancer cells
Antitumor activities of an oncolytic adenovirus equipped with a double siRNA targeting Ki67 and hTERT in renal cancer cells
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配备双 siRNA 的溶瘤腺病毒靶向 Ki67 和 hTERT 在肾癌细胞中的抗肿瘤活性
DOI：
10.1016/j.virusres.2013.12.021
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发表时间：
2014-03-06
期刊：
影响因子：
5
通讯作者：
Zheng, Junnian
中科院分区：
文献类型：
--
作者：
Fang, Lin;Cheng, Qian;Zheng, Junnian
RNA干扰已被证明是基因敲除的有力工具。我们以前的研究表明，腺病毒携带的Ki 67 shRNA降低了Ki 67的表达。在这项研究中，我们构建了新的溶瘤腺病毒，其中1067核心启动子驱动E1 A基因的表达。这些腺病毒配备有Ki 67小干扰RNA（siRNA）、人端粒酶逆转录酶（hTERT）siRNA或靶向Ki 67和hTERT的双siRNA。我们鉴定了溶瘤腺病毒在3种肾癌细胞系、人正常肾小管细胞HK-2和荷KETR-3异种移植瘤的裸鼠中的抗肿瘤活性。我们的研究结果表明，这些溶瘤腺病毒，特别是Ki 67-ZXC 2-双siRNA，可以有效地诱导Ki 67和hTERT基因的沉默，允许有效的病毒复制，并在体外和裸鼠中诱导肾癌细胞的显著凋亡。我们的结论是，双siRNA介导的溶瘤病毒治疗可能是一个有效的策略，癌症基因治疗。(C)2013爱思唯尔有限公司版权所有。
RNA interference has been proven to be a powerful tool for gene knockdown. Our previous study demonstrated that a Ki67 shRNA carried by an adenovirus reduced Ki67 expression. In this study, we constructed novel oncolytic adenoviruses in which the 1067 core promoter drove expression of the E1A gene. These adenoviruses were equipped with either a Ki67 small interfering RNA (siRNA), a human telomerase reverse transcriptase (hTERT) siRNA or a double siRNA targeting Ki67 and hTERT. We identified the antitumor activities of oncolytic adenoviruses in 3 renal cancer cell lines, human normal renal tube cell HK-2 and also in nude mice bearing KETR-3-xenografted tumors. Our results showed that these oncolytic adenoviruses, especially Ki67-ZXC2-double siRNA, could effectively induce silencing of the Ki67 and hTERT genes, allow efficient viral replication and induce significant apoptosis of renal cancer cells in vitro and in nude mice. We concluded that a dual siRNA mediated by oncolytic virotherapy could be an effective strategy for cancer gene therapy. (C) 2013 Elsevier B.V. All rights reserved.