Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice.
Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice.
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DOI：
10.1186/s12885-015-1731-x
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发表时间：
2015-10-16
期刊：
影响因子：
3.8
通讯作者：
Zhou HS
中科院分区：
文献类型：
--
作者：
Cheng PH;Rao XM;Wechman SL;Li XF;McMasters KM;Zhou HS
临床试验表明，小鼠模型中人类肿瘤异种移植的临床前结果可能夸大了腺病毒（Ad）介导的溶瘤治疗的潜力。我们之前已经证明，人类ad的复制依赖于癌细胞中周期蛋白E的失调或过度表达。利用转人细胞周期蛋白E过表达引发小鼠肺腺癌的ED-1细胞，可用于研究溶瘤性ad的抗肿瘤效果。利用Ad-cycE靶向细胞周期蛋白E过表达的ED-1细胞，在同基因小鼠模型中抑制肿瘤生长，研究溶瘤病毒治疗方法。小鼠ED-1细胞允许人Ad复制，Ad- cyce抑制免疫活性FVB小鼠ED-1肿瘤生长。肿瘤中被溶瘤性ad破坏的ED-1细胞被包膜状结构包裹，而包膜外的细胞未被感染并存活。在同基因小鼠模型中，Ad-cycE可以靶向癌细胞中cyclin E的过度表达，抑制肿瘤生长。瘤内注射Ad后形成的囊状结构可以防止病毒颗粒扩散到整个肿瘤。本文的在线版本（doi:10.1186/s12885-015-1731-x）包含补充材料，授权用户可以使用。
Clinical trials have indicated that preclinical results obtained with human tumor xenografts in mouse models may overstate the potential of adenovirus (Ad)-mediated oncolytic therapies. We have previously demonstrated that the replication of human Ads depends on cyclin E dysregulation or overexpression in cancer cells. ED-1 cell derived from mouse lung adenocarcinomas triggered by transgenic overexpression of human cyclin E may be applied to investigate the antitumor efficacy of oncolytic Ads. Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies. Murine ED-1 cells were permissive for human Ad replication and Ad-cycE repressed ED-1 tumor growth in immunocompetent FVB mice. ED-1 cells destroyed by oncolytic Ads in tumors were encircled in capsule-like structures, while cells outside the capsules were not infected and survived the treatment. Ad-cycE can target cyclin E overexpression in cancer cells and repress tumor growth in syngeneic mouse models. The capsule structures formed after Ad intratumoral injection may prevent viral particles from spreading to the entire tumor. The online version of this article (doi:10.1186/s12885-015-1731-x) contains supplementary material, which is available to authorized users.