Haliotis discus discus Sialic Acid-Binding Lectin Reduces the Oncolytic Vaccinia Virus Induced Toxicity in a Glioblastoma Mouse Model.

Haliotis discus discus Sialic Acid-Binding Lectin Reduces the Oncolytic Vaccinia Virus Induced Toxicity in a Glioblastoma Mouse Model.
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七彩鲍唾液酸结合凝集素可降低胶质母细胞瘤小鼠模型中溶瘤牛痘病毒诱导的毒性

DOI:
10.3390/md16050141
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发表时间:
2018-04-26
期刊:
影响因子:
5.4
通讯作者:
Luo J
Luo J
中科院分区:
医学2区
文献类型:
--
作者:
Li G;Mei S;Cheng J;Wu T;Luo J

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尽管溶瘤病毒为癌症治疗提供了有吸引力的载体,但它们的副作用在很大程度上被忽视了。在这项工作中,大鼠C6胶质母细胞瘤细胞皮下异种移植到小鼠,胸苷激酶缺陷型溶瘤痘苗病毒(oncVV)在这个模型中诱导严重的毒性。然而,oncVV-HddSBL,其中一个基因编码盘鲍唾液酸结合凝集素(HddSBL)插入到oncVV,显着延长小鼠的生存期相比,控制病毒。HddSBL能降低肿瘤细胞分泌的IL-2水平,促进肿瘤细胞增殖,抑制肿瘤细胞抗病毒因子的表达。此外,HddSBL下调组蛋白H3和H4的表达水平,并上调组蛋白H3 R8和H4 R3不对称二甲基化,证实了HddSBL对染色质结构的影响所建议的转录组数据。我们的研究结果可能会提供见解利用HddSBL在抵消溶瘤痘苗病毒的不良反应。
Although oncolytic viruses provide attractive vehicles for cancer treatment, their adverse effects are largely ignored. In this work, rat C6 glioblastoma cells were subcutaneously xenografted into mice, and a thymidine kinase-deficient oncolytic vaccinia virus (oncoVV) induced severe toxicity in this model. However, oncoVV-HddSBL, in which a gene encoding Haliotis discus discus sialic acid-binding lectin (HddSBL) was inserted into oncoVV, significantly prolonged the survival of mice as compared to the control virus. HddSBL reduced the tumor secreted serum rat IL-2 level upregulated by oncoVV, promoted viral replication, as well as inhibited the expression of antiviral factors in C6 glioblastoma cell line. Furthermore, HddSBL downregulated the expression levels of histone H3 and H4, and upregulated histone H3R8 and H4R3 asymmetric dimethylation, confirming the effect of HddSBL on chromatin structure suggested by the transcriptome data. Our results might provide insights into the utilization of HddSBL in counteracting the adverse effects of oncolytic vaccinia virus.
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表达可分泌的三聚体trigg的低氧和端粒酶反应性肿瘤腺病毒会触发肿瘤特异性细胞凋亡,并促进耐痕量的胶质母细胞瘤中的病毒分散体。
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