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评估牛疱疹病毒 4 型在人神经胶质瘤和乳腺癌细胞中的复制作为一种潜在的溶瘤病毒。

Assessment of replication of bovine herpesvirus type 4 in human glioblastoma and breast cancer cells as a potential oncolytic virus.

机构信息

Division of Infectious Diseases and International Medicine (IDIM), University of Minnesota Twin Cities, Minneapolis, MN, USA.

Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara, Turkey.

出版信息

Virus Genes. 2021 Feb;57(1):31-39. doi: 10.1007/s11262-020-01802-z. Epub 2020 Oct 26.

DOI:10.1007/s11262-020-01802-z
PMID:33104955
Abstract

Oncolytic viruses have been extensively used in cancer treatment due to their tropism, selective replication only in tumor cells, and possible synergic interaction with other therapeutics. Different researchers have demonstrated that bovine herpesvirus 4 (BoHV-4), a member of the gammaherpesviridae family, has oncolytic potential in some human-origin cancer cell lines like glioma through the selective replication strategy. Using four apoptosis detection methods, namely MTT, LDH, TUNEL, and Annexin V assays, we evaluated the apoptotic effect of BoHV-4 Movar33/63 reference strain along with a recombinant BoHV-4 expressing EGFP in U87 MG cells (human glioblastoma cell line), MDA MB-231 (human breast cancer cell line), and MCF10a (non-tumorigenic human mammary epithelial cell line). Our findings indicate that this virus can replicate and induce apoptosis in these cell lines and hinder in vitro proliferation in a dose-dependent manner. In conclusion, BoHV-4 has in vitro potential as a novel oncolytic virus in human cancer therapy. However, its replication potential in the MCF10a cells as a non-tumorigenic human mammary epithelial cell line is a concern in using this virus in cancer therapy, at least against human mammary tumors. Further studies must therefore be conducted to examine the specific apoptotic pathways induced by this virus to move on to further experiments.

摘要

溶瘤病毒由于其对肿瘤的趋向性、仅在肿瘤细胞中选择性复制以及与其他治疗方法可能的协同作用,已被广泛应用于癌症治疗。不同的研究人员已经证明,属于γ疱疹病毒科的牛疱疹病毒 4(BoHV-4)通过选择性复制策略在一些源自人类的癌细胞系(如神经胶质瘤)中具有溶瘤潜力。我们使用四种凋亡检测方法,即 MTT、LDH、TUNEL 和 Annexin V 检测,评估了 BoHV-4 Movar33/63 参考株以及表达 EGFP 的重组 BoHV-4 在 U87 MG 细胞(人神经胶质瘤细胞系)、MDA MB-231(人乳腺癌细胞系)和 MCF10a(非致瘤性人乳腺上皮细胞系)中的凋亡效应。我们的研究结果表明,该病毒可以在这些细胞系中复制并诱导凋亡,并以剂量依赖的方式阻碍体外增殖。总之,BoHV-4 具有作为人类癌症治疗新型溶瘤病毒的体外潜力。然而,其在 MCF10a 细胞(非致瘤性人乳腺上皮细胞系)中的复制潜力是在癌症治疗中使用该病毒的一个关注点,至少在针对人类乳腺肿瘤方面是如此。因此,必须进行进一步的研究来检查该病毒诱导的特定凋亡途径,以推进进一步的实验。

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