Ginting Teridah Ernala, Suryatenggara Jeremiah, Christian Salomo, Mathew George
Division of Immunology, Mochtar Riady Institute for Nanotechnology and Medical Science Group, University of Pelita Harapan, Tangerang, Indonesia.
Oncolytic Virother. 2017 Mar 3;6:21-30. doi: 10.2147/OV.S123292. eCollection 2017.
To investigate the specific role of immune responses induced by lentogenic Newcastle disease virus (NDV) for its antitumor effect.
NDV LaSota strain was used to infect the following human cells: non-small cell lung carcinoma (A549), glioblastoma (U87MG and T98G), mammary gland adenocarcinoma (MCF7 and MDA-MB-453), hepatocellular carcinoma (Huh7), transformed embryonic kidney cells (HEK293), primary monocytes, lung fibroblast (HF19), skin fibroblast (NB1RGB) and rat astroglia (RCR-1) at 0.001 multiplicity of infection. NDV-induced cytotoxicity and expression of proinflammatory cytokines were analyzed using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and multiplex enzyme-linked immunosorbent assay, respectively.
Tumor cells (A549, U87MG, T98G, Huh7, MDA-MB-453, and MCF7) showed viability of <44%, while normal cell lines HEK293, NB1RGB, and RCR-1 showed 84%, 73%, and 69% viability at 72 hours postinfection, respectively. Proinflammatory cytokine profiling showed that NDV mainly induced the secretion of interferon (IFN)-α, IFN-β, and IFN-λ in tumor cells and only IFN-λ in normal cells. In addition, NDV infection induced the production of interleukin (IL)-6 in most cells.
Our findings suggest a new perspective regarding the role of IFN-λ and IL-6 in the mechanism of tumor selectivity and oncolysis of NDV.
研究弱毒新城疫病毒（NDV）诱导的免疫反应在其抗肿瘤作用中的具体作用。
使用NDV LaSota株感染以下人类细胞：非小细胞肺癌（A549）、胶质母细胞瘤（U87MG和T98G）、乳腺腺癌（MCF7和MDA-MB-453）、肝细胞癌（Huh7）、转化的胚胎肾细胞（HEK293）、原代单核细胞、肺成纤维细胞（HF19）、皮肤成纤维细胞（NB1RGB）和大鼠星形胶质细胞（RCR-1），感染复数为0.001。分别使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐法和多重酶联免疫吸附测定法分析NDV诱导的细胞毒性和促炎细胞因子的表达。
肿瘤细胞（A549、U87MG、T98G、Huh7、MDA-MB-453和MCF7）在感染后72小时的活力<44%，而正常细胞系HEK293、NB1RGB和RCR-1的活力分别为84%、73%和69%。促炎细胞因子分析表明，NDV主要诱导肿瘤细胞中干扰素（IFN）-α、IFN-β和IFN-λ的分泌，而在正常细胞中仅诱导IFN-λ的分泌。此外，NDV感染在大多数细胞中诱导白细胞介素（IL）-6的产生。
我们的研究结果为IFN-λ和IL-6在NDV肿瘤选择性和溶瘤机制中的作用提供了新的视角。
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