Combing oncolytic adenovirus expressing Beclin-1 with chemotherapy agent doxorubicin synergistically enhances cytotoxicity in human CML cells in vitro
Combing oncolytic adenovirus expressing Beclin-1 with chemotherapy agent doxorubicin synergistically enhances cytotoxicity in human CML cells in vitro
复制标题
将表达 Beclin-1 的溶瘤腺病毒与化疗药物阿霉素相结合可协同增强体外人 CML 细胞的细胞毒性。
DOI：
10.1038/aps.2017.100
复制
发表时间：
2018-02-01
影响因子：
8.2
通讯作者：
Qian, Wen-bin
中科院分区：
文献类型：
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作者：
Li, Li;You, Liang-shun;Qian, Wen-bin
癌症病毒治疗提供了一种通过溶瘤直接杀死癌细胞的治疗癌症的新策略。将治疗基因插入到修饰腺病毒的基因组中，从而创造一种所谓的基因-病毒疗法，它共享基因疗法和病毒疗法的优点。在这项研究中，我们研究了一种结合腺病毒载体的溶瘤作用和同时表达自噬基因Beclin-1的策略是否为化疗耐药的慢性髓性白血病（CML）细胞提供了治疗优势，并在体外评估了SG511-BECN和阿霉素（Dox）在人CML细胞中的协同作用。将Beclin-1基因导入溶瘤腺病毒主干，构建溶瘤病毒SG511-BECN。SG511-BECN对多药耐药CML细胞株K562/A02的抗白血病活性显著提高，这是通过诱导细胞自噬死亡介导的。此外，Dox可以与SG511-BECN协同杀死CML细胞，通过提高溶瘤腺病毒的感染效率，而不会对正常的人单核细胞造成明显损伤。结果表明，靶向自噬细胞死亡途径和化疗药物与溶瘤腺病毒联合治疗化疗耐药白血病可能是一种新的治疗策略。
Cancer virotherapy provides a new strategy to treat cancer that can directly kill cancer cells by oncolysis. Insertion of therapeutic genes into the genome of a modified adenovirus, thereby creating a so-called gene-virotherapy that shares the advantages of gene therapy and virotherapy. In this study we investigated whether a strategy that combines the oncolytic effects of an adenoviral vector with the simultaneous expression of the autophagy gene Beclin-1 offered a therapeutic advantage for chronic myeloid leukemia (CML) cells with resistance to chemotherapy and evaluated the synergistic effects of SG511-BECN and doxorubicin (Dox) in human CML cells in vitro. Oncolytic virus SG511-BECN was constructed through introducing the Beclin-1 gene into the oncolytic adenoviral backbone. SG511-BECN displayed significantly improved antileukemia activity on multidrug-resistant CML cell line K562/A02, which was mediated via induction of autophagic cell death. Furthermore, Dox could synergize with SG511-BECN to kill the CML cells by improving the infectious efficiency of the oncolytic adenovirus without causing significant damage to normal human mononuclear cells. The results demonstrate that targeting the autophagic cell death pathway and combination of a chemotherapy agent with oncolytic adenovirus may be a novel strategy for the treatment of leukemia with chemotherapy resistance.