Enhancing therapeutic efficacy of oncolytic vaccinia virus armed with Beclin-1, an autophagic Gene in leukemia and myeloma
Enhancing therapeutic efficacy of oncolytic vaccinia virus armed with Beclin-1, an autophagic Gene in leukemia and myeloma
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增强携带自噬基因 Beclin-1 的溶瘤牛痘病毒对白血病和骨髓瘤的治疗效果
DOI：
10.1016/j.biopha.2020.110030
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发表时间：
2020-05-01
影响因子：
7.5
通讯作者：
Qian, Wenbin
中科院分区：
文献类型：
--
作者：
Lei, Wen;Wang, Shibing;Qian, Wenbin
人们采取了不同的策略来使病毒疗法更有效地杀死癌细胞。其中，携带治疗基因以增强抗肿瘤活性的溶瘤病毒是一种流行的方法。在这项研究中，测试了一种新开发的表达 Beclin-1 (OVV-BECN1) 的溶瘤痘苗病毒 (OVV) 在血癌中的体外和体内溶瘤活性。结果显示OVV对白血病细胞表现出较高的感染性。 OVV-BECN1 在野生型白血病和多发性骨髓瘤 (MM) 细胞系或 caspase-3 shRNA 白血病细胞系中诱导显着的不依赖于凋亡的细胞死亡，并且与亲本 OVV 相比具有优异的抗肿瘤活性。 OVV-BECN1 诱导的自噬细胞死亡已在体外和体内实验中得到证实。最后，OVV-BECN1 对 III 类组蛋白脱乙酰酶成员 SIRT-1 的上调导致 LC3 脱乙酰化及其从细胞核向细胞质的分布，这可能有助于诱导自噬。总体而言，我们的数据表明，溶瘤痘苗病毒通过溶瘤和自噬机制对血癌具有良好的治疗效果，因此可能构成治疗人类白血病和多发性骨髓瘤的一种有前途且有效的治疗策略。然而，其可靠的临床转化还需要进一步的研究。
Different strategies were taken to make virotherapy more effective at killing cancer cells. Among them, oncolytic virus which arms the therapeutic gene to enhance antitumor activity is a prevalent approach. In this study, a newly developed oncolytic vaccinia virus (OVV) that expresses Beclin-1 (OVV-BECN1) was tested for its in vitro and in vivo oncolytic activity in blood cancer. Results showed that the OVV exhibited higher infectivity for leukemia cells. OVV-BECN1 induced significant apoptosis-independent cell death either in wild-type leukemia and multiple myeloma (MM) cell lines or caspase-3 shRNA leukemia cell lines, and had a superior antitumor activity compared to the parent OVV. Autophagic cell death induced by OVV-BECN1 was demonstrated in vitro and in vivo experiments. Finally, upregulation of SIRT-1, a member of class III histone deacetylases, by OVV-BECN1 resulted in the deacetylation of LC3 and its distribution from the nucleus toward the cytoplasm, which might contribute to induction of autophagy. Overall, our data showed a favorable therapeutic effect of the oncolytic vaccinia virus on blood cancers through oncolytic and autophagic mechanisms, and may therefore constitute a promising and effective therapeutic strategy for treating human leukemia and MM. However, further studies are warranted for its reliable clinical translation.