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Antitumor effect of the Newcastle disease viral hemagglutinin-neuraminidase gene is expressed through an oncolytic adenovirus effect in osteosarcoma cells

机译:新城疫病毒血凝素 - 神经氨酸酶基因的抗肿瘤效应通过骨肉瘤细胞的溶血性腺病毒作用表示

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摘要

Newcastle disease virus (NDV) can specifically kill cancer cells and has less toxicity to normal cells. The hemagglutinin-neuraminidase (HN) protein is an important structural protein in NDV pathogenesis and has been postulated as a promising candidate for antitumor therapy. The aim of this study was to investigate the anticancer potential of recombinant adenovirus Ad-HN-PEG3p-E1a. An MTS assay was performed to determine viral proliferation after viral infection, the data showed that the proliferation ability of osteosarcoma cells decreased, whereas there was no significant change in normal hepatic cells. DAPI and Annexin V experiments showed that osteosarcoma cells were killed because of apoptosis, active oxygen content, and augmented mitochondrial membrane potential loss. Caspase Activity Assay Kits were used to detect the caspase-3 activities of the treated OS-732 for increased expression. Western blot analysis showed that cytochrome C increased significantly and apoptosis of the virus was confirmed in tumor cells. In-vivo experiments show that NDV has an inhibitory effect on tumor growth. The recombinant adenovirus, which is composed of a HN protein and progressive increment promoter PEG3p, could inhibit the growth of OS-732 and promote the apoptosis of tumor cells. However, there was no clear relationship with normal cell (L02) apoptosis.
机译:新城疫病毒(NDV)可以特异性杀死癌细胞并对正常细胞具有较小的毒性。血血糖素 - 神经氨酸酶(HN)蛋白是NDV发病机制中重要的结构蛋白,已被假定为抗肿瘤治疗的有希望的候选物。本研究的目的是探讨重组腺病毒Ad-HN-PEG3P-E1A的抗癌潜力。进行MTS测定以确定病毒感染后的病毒增殖,数据显示,骨肉瘤细胞的增殖能力降低,而常规肝细胞没有显着变化。 DAPI和Annexin V实验表明,由于凋亡,活性氧含量和增强线粒体膜电位损失,骨肉瘤细胞被杀死。 Caspase活性测定试剂盒用于检测处理过的OS-732的Caspase-3活性,用于增加表达。 Western印迹分析表明,细胞色素C显着增加,病毒的凋亡在肿瘤细胞中确认。体内实验表明,NDV对肿瘤生长具有抑制作用。由HN蛋白和渐进式增量启动子PEG3P组成的重组腺病毒可以抑制OS-732的生长并促进肿瘤细胞的凋亡。然而,与正常细胞(L02)凋亡没有明显的关系。

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