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首页> 美国卫生研究院文献>Oncotarget >Apoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression
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Apoptin enhances the oncolytic properties of vaccinia virus and modifies mechanisms of tumor regression

机译：Apoptin增强痘苗病毒的溶瘤特性并改变肿瘤消退的机制

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摘要

A recombinant vaccinia virus VVdGF-ApoS24/2 expressing apoptin selectively kills human cancer cells in vitro [Kochneva et al., 2013]. We compared the oncolytic activity of this recombinant with that of the parental strain L-IVP using a model of human A431 carcinoma xenografts in nude mice. Single intratumoral injections (2×107 PFU/mouse) of the viruses produced a dramatic decrease in tumor volumes, which was higher after injection of apoptin-producing virus. The tumor dried out after the injection of recombinant while injection of L-IVP strain resulted in formation of cavities filled with cell debris and liquid. Both viruses rapidly spread in xenografts and replicate exclusively in tumor cells causing their destruction within 8 days. Both viruses induced insignificant level of apoptosis in tumors. Unlike the previously described nuclear localization of apoptin in cancer cells the apoptin produced by recombinant virus was localized to the cytoplasm. The apoptin did not induce a typical apoptosis, but it rather influenced pathway of cell death and thereby caused tumor shrinkage. The replacement of destroyed cells by filamentous material is the main feature of tumor regression caused by the VVdGF-ApoS24/2 virus. The study points the presence of complicated mechanisms of apoptin effects at the background of vaccinia virus replication.
机译：表达凋亡蛋白的重组牛痘病毒V​​VdGF-ApoS24 / 2在体外选择性杀死人癌细胞[Kochneva等，2013]。我们使用裸鼠中人A431癌异种移植物模型比较了该重组体与亲本菌株L-IVP的溶瘤活性。病毒的肿瘤内单次注射（2×10 7 PFU /小鼠）使肿瘤体积显着减少，而注射促凋亡素的病毒注射后则更高。注射重组体后肿瘤变干，而注射L-IVP株导致形成充满细胞碎片和液体的腔。两种病毒都在异种移植物中迅速传播，并仅在肿瘤细胞中复制，导致它们在8天内被破坏。两种病毒均在肿瘤中诱导了微不足道的细胞凋亡水平。与先前描述的凋亡素在癌细胞中的核定位不同，重组病毒产生的凋亡素被定位在细胞质中。细胞凋亡蛋白不诱导典型的细胞凋亡，而是影响细胞死亡的途径，从而引起肿瘤缩小。由VVdGF-ApoS24 / 2病毒引起的肿瘤消退的主要特征是用丝状材料替代破坏的细胞。该研究指出了牛痘病毒复制背景下凋亡蛋白作用复杂机制的存在。

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