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通过 Orf 病毒株 NA1/11 在结直肠癌细胞中的体外和体内溶瘤作用鉴定。

Identification of in vitro and in vivo oncolytic effect in colorectal cancer cells by Orf virus strain NA1/11.

机构信息

Key Laboratory of Antibody Engineering of Guangdong Higher Education Institutes, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Department of Laboratory Medicine, School of Stomatology and Medicine, Foshan University, Foshan, Guangdong 528000, P.R. China.

出版信息

Oncol Rep. 2021 Feb;45(2):535-546. doi: 10.3892/or.2020.7885. Epub 2020 Dec 8.

Abstract

Orf virus (ORFV) is a favorable oncolytic viral carrier in research, and ORFV strain NZ2 has been revealed to have antitumor effects in animal models mediated by immunoregulation profile. However, the antitumor effects triggered by the ORFV in colorectal cancer (CRC) cells is poorly characterized. The in vivo and in vitro roles of ORFV in CRC were determined using western blotting, colony formation, CCK‑8, wound scratch assay, qPCR, and animal models. Furthermore, cytokine antibody chip assay, flow cytometry, western blotting, and immunohistochemical (IHC) assays were conducted to explore the potential mechanism of ORFV. The present data revealed that ORFV strain NA1/11 infected and inhibited the in vitro growth and migration of CRC cells. By establishing a CRC model in Balb/c mice, it was revealed that ORFV strain NA1/11 significantly inhibited the in vivo growth and migration of CRC cells. A cytokine antibody array was utilized to obtain a more comprehensive profile revealing the differentially expressed cytokines in ORFV infection. Cytokines, such as IL‑7, IL‑13, IL‑15, CD27, CD30, pentraxin 3, and B lymphocyte chemoattractant (BLC), were upregulated. Axl, CXCL16, ANG‑3, MMP10, IFN‑γ R1 and VEGF‑B were downregulated. The results indicated that ORFV played roles in the regulation of key factors relevant to apoptosis, autoimmunity/inflammation, angiogenesis, and the cell cycle. Finally, data was presented to validate that ORFV infection induces oncolytic activity by enhancing apoptosis in vivo and in vitro. In conclusion, ORFV could be an oncolytic virus for CRC therapy.

摘要

口疮病毒(ORFV)是一种很有前途的溶瘤病毒载体,在研究中,ORFV 株 NZ2 已被证明通过免疫调节谱在动物模型中具有抗肿瘤作用。然而,ORFV 在结直肠癌(CRC)细胞中引发的抗肿瘤作用尚未得到很好的描述。本研究通过 Western blot 印迹、集落形成、CCK-8、划痕实验、qPCR 和动物模型,确定了 ORFV 在 CRC 中的体内和体外作用。此外,还进行了细胞因子抗体芯片分析、流式细胞术、Western blot 印迹和免疫组织化学(IHC)检测,以探讨 ORFV 的潜在机制。本研究数据表明,ORFV 株 NA1/11 感染并抑制 CRC 细胞的体外生长和迁移。通过在 Balb/c 小鼠中建立 CRC 模型,揭示了 ORFV 株 NA1/11 显著抑制 CRC 细胞的体内生长和迁移。利用细胞因子抗体芯片获得了更全面的图谱,揭示了 ORFV 感染中差异表达的细胞因子。上调的细胞因子包括 IL-7、IL-13、IL-15、CD27、CD30、五聚素 3 和 B 淋巴细胞趋化因子(BLC)。下调的细胞因子包括 Axl、CXCL16、ANG-3、MMP10、IFN-γR1 和 VEGF-B。结果表明,ORFV 在调节与细胞凋亡、自身免疫/炎症、血管生成和细胞周期相关的关键因素中发挥作用。最后,数据表明 ORFV 通过增强体内和体外的细胞凋亡来诱导溶瘤活性。综上所述,ORFV 可能成为 CRC 治疗的溶瘤病毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de5/7757097/4e003b900c2c/OR-45-02-0535-g00.jpg

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