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Assessment of replication of bovine herpesvirus type 4 in human glioblastoma and breast cancer cells as a potential oncolytic virus
Virus Genes ( IF 1.9 ) Pub Date : 2020-10-26 , DOI: 10.1007/s11262-020-01802-z
Touraj Aligholipour Farzani 1 , Seval Bilge Dagalp 2 , Aykut Ozkul 2, 3 , Hakan Gurdal 4 , Firat Dogan 5 , Feray Alkan 2
Affiliation  

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.



中文翻译:

评估牛疱疹病毒 4 型在人胶质母细胞瘤和乳腺癌细胞中作为潜在溶瘤病毒的复制

由于溶瘤病毒的趋向性、仅在肿瘤细胞中的选择性复制以及可能与其他疗法的协同相互作用,溶瘤病毒已被广泛用于癌症治疗。不同的研究者已经证明,牛疱疹病毒4(BoHV-4),所述的构件gammaherpesviridae家族,通过选择性复制策略在某些人源癌细胞系(如胶质瘤)中具有溶瘤潜力。使用四种凋亡检测方法,即 MTT、LDH、TUNEL 和膜联蛋白 V 测定,我们评估了 BoHV-4 Movar33/63 参考菌株以及表达 EGFP 的重组 BoHV-4 在 U87 MG 细胞(人胶质母细胞瘤细胞系)中的凋亡作用)、MDA MB-231(人乳腺癌细胞系)和 MCF10a(非致瘤性人乳腺上皮细胞系)。我们的研究结果表明,这种病毒可以在这些细胞系中复制和诱导细胞凋亡,并以剂量​​依赖性方式阻碍体外增殖。总之,BoHV-4 在体外具有作为人类癌症治疗中新型溶瘤病毒的潜力。然而,作为非致瘤性人类乳腺上皮细胞系,它在 MCF10a 细胞中的复制潜力是将该病毒用于癌症治疗的一个问题,至少是针对人类乳腺肿瘤。因此,必须进行进一步的研究以检查由该病毒诱导的特定细胞凋亡途径,以进行进一步的实验。

更新日期:2020-10-30
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