Abstract

Oncolytic Newcastle disease viruses (NDVs) make up a group of antitumor agents for the experimental treatment of oncological diseases that nonpathogenic for human beings. It is known that realization of the cytotoxic effect of NDV strains on the tumor cells depends on the peculiarities of viral genome structure, strain virulence, and tumor cell culture (National Institutes of Health, 2018). At the same time, the mechanism of NDV-induced death has been poorly studied. The aim of this work was to study the nature of morphological changes in HeLa and Hep-2 (HeLa derivative) human tumor cells after infection with the wild-type mesogenic NDV strain NDV/Altai/pigeon/770/2011. The calculation of living tumor cells using MTT test demonstrated that the cytotoxic activity of NDV/Altai/pigeon/770/2011 strain in 144 h after infection decreases the cell viability till 13.08 ± 8.29% (HeLa) and 4.74 ± 3.29% (Hep-2, HeLa derivative). A routine staining detected morphological traits of degradation of infected cells, while morphometric studies detected an increase in the value of the nuclear–cytoplasmic ratio (NCR). The presence of a virus in the tumor cells was visualized by the method of immunocytochemical staining (ICS) using antibodies to the HN glycoprotein of the NDV envelope. The results of immunodetection of tumor necrosis factor α (TNFα) suggest the activation of cell death along the apoptosis pathway against the background of viral infection. The results obtained indicate a pronounced cytotoxic activity of wild-type NDV/Altai/pigeon/770/2011 strain regarding HeLa and Hep-2 (HeLa derivative) adenocarcinoma cells and sensitivity of the studied cell lines to the oncolytic effect of NDV.

中文翻译：

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野生型新城疫病毒株对肿瘤细胞的体外细胞毒作用

摘要

溶瘤新城疫病毒（NDV）组成了一组抗肿瘤药物，用于实验性治疗对人类无致病性的肿瘤疾病。已知NDV菌株对肿瘤细胞的细胞毒性作用的实现取决于病毒基因组结构，菌株毒力和肿瘤细胞培养的独特性（National Institutes of Health，2018）。同时，对NDV致死的机制的研究还很少。这项工作的目的是研究野生型介导NDV毒株NDV / Altai / pigeon / 770/2011感染后HeLa和Hep-2（HeLa衍生物）人肿瘤细胞形态变化的性质。使用MTT测试计算活肿瘤细胞显示，NDV / Altai / pigeon / 770/2011菌株在感染后144小时内的细胞毒性活性将细胞活力降低至13.08±8.29％（HeLa）和4.74±3.29％（Hep- 2，HeLa导数）。常规染色检测到感染细胞降解的形态特征，而形态计量学研究则检测到核质比（NCR）值增加。使用针对NDV包膜的HN糖蛋白的抗体，通过免疫细胞化学染色（ICS）方法可观察到肿瘤细胞中病毒的存在。肿瘤坏死因子α（TNFα）的免疫检测结果表明，在病毒感染的背景下，沿凋亡途径的细胞死亡被激活。