Oncolytic Bovine Herpesvirus 1 Inhibits Human Lung Adenocarcinoma A549 Cell Proliferation and Tumor Growth by Inducing DNA Damage.
Oncolytic Bovine Herpesvirus 1 Inhibits Human Lung Adenocarcinoma A549 Cell Proliferation and Tumor Growth by Inducing DNA Damage.
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溶瘤牛疱疹病毒 1 通过诱导 DNA 损伤抑制人肺腺癌 A549 细胞增殖和肿瘤生长
DOI：
10.3390/ijms22168582
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发表时间：
2021-08-10
影响因子：
5.6
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Qiu W;Ding X;Li S;He Y;Zhu L
牛疱疹病毒1 （BoHV-1）是一种具有广泛抗肿瘤谱的有前途的溶瘤病毒；但其体内对人肺腺癌的溶瘤作用尚未见报道。在本研究中，我们报道了BoHV-1可以作为人肺腺癌的溶瘤病毒，并阐明了BoHV-1抑制肿瘤细胞增殖和生长的潜在机制。首先，我们检测了BoHV-1在人肺腺癌A549细胞中的溶瘤活性。BoHV-1感染降低了组蛋白去乙酰化酶（hdac）的蛋白水平，包括有希望的抗肿瘤药物靶点hdac -1。此外，HDAC抑制剂Trichostatin A （TSA）促进BoHV-1感染，加重DNA损伤和细胞病理，提示BoHV-1与TSA之间存在协同作用。在A549肿瘤异种移植小鼠模型中，我们首次发现BoHV-1可以感染肿瘤并抑制肿瘤生长，其疗效与治疗TSA相似，并且hdac对病毒复制有潜在的影响。综上所述，我们的研究表明BoHV-1在体内对人肺腺癌具有溶瘤作用。
Bovine herpesvirus 1 (BoHV-1) is a promising oncolytic virus with broad antitumor spectrum; however, its oncolytic effects on human lung adenocarcinoma in vivo have not been reported. In this study, we report that BoHV-1 can be used as an oncolytic virus for human lung adenocarcinoma, and elucidate the underlying mechanism of how BoHV-1 suppresses tumor cell proliferation and growth. First, we examined the oncolytic activities of BoHV-1 in human lung adenocarcinoma A549 cells. BoHV-1 infection reduced the protein levels of histone deacetylases (HDACs), including HDAC1-4 that are promising anti-tumor drug targets. Furthermore, the HDAC inhibitor Trichostatin A (TSA) promoted BoHV-1 infection and exacerbated DNA damage and cytopathology, suggesting a synergy between BoHV-1 and TSA. In the A549 tumor xenograft mouse model, we, for the first time, showed that BoHV-1 can infect tumor and suppressed tumor growth with a similar high efficacy as the treatment of TSA, and HDACs have potential effects on the virus replication. Taken together, our study demonstrates that BoHV-1 has oncolytic effects against human lung adenocarcinoma in vivo.
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影响因子：
14.9
作者：
Roos WP;Krumm A
通讯作者：
Krumm A
DOI：
10.1099/vir.0.83272-0
发表时间：
2008-01
期刊：
The Journal of general virology
影响因子：
--
作者：
Coleman HM;Connor V;Cheng ZSC;Grey F;Preston CM;Efstathiou S
通讯作者：
Efstathiou S
影响因子：
6.4
作者：
Cuddington, B. P.;Dyer, A. L.;Mossman, K. L.
通讯作者：
Mossman, K. L.
影响因子：
7.2
作者：
Fiorito, Filomena;Marfe, Gabriella;Pagnini, Ugo
通讯作者：
Pagnini, Ugo
影响因子：
5.6
作者：
Sun, Yu;Luo, Jiping;Ke, Zunfu
通讯作者：
Ke, Zunfu