Peng Jiamin, Wang Shibing, Fan Weimin, Li Shuangshuang, Wu Yi, Mou Xiaozhou, Wang Jianchao, Tong Xiangmin
The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China,
Clinical Research Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China,
Onco Targets Ther. 2018 Oct 15;11:6887-6900. doi: 10.2147/OTT.S172037. eCollection 2018.
In consideration of the drug resistance and side effects associated with cytarabine, one of the most effective drugs for the treatment of acute myeloid leukemia (AML), there is a need for safer and effective strategies.
In the present investigation, we fabricated a new oncolytic vaccinia virus (oVV-), which expresses the inhibitor of growth family member 4 () and explored its antitumor activity individually and in combination with cytarabine in AML cells.
The experiments confirmed that oVV can efficiently and specifically infect leukemia cells, and augment the gene expression. Flow cytometry and western blot demonstrated that oVV- enhances apoptosis and G2/M phase arrest in AML cells, and causes remarkable cancer cell death. In addition, the synergistic efficiency of oVV- and cytarabine was investigated in vitro and in vivo; the combination significantly inhibited the survival of leukemia cells in vitro and xenografted KG-1 AML tumor growth in vivo.
In brief, oVV- can increase the sensitivity of leukemia cells to cytarabine and induce cell apoptosis in vitro and in vivo. Thus, oVV- may be a promising therapeutic candidate for leukemia and in combination with cytarabine represents a potential antitumor therapy.
鉴于阿糖胞苷（治疗急性髓系白血病（AML）最有效的药物之一）存在耐药性和副作用，需要更安全有效的治疗策略。
在本研究中，我们构建了一种新的表达生长抑制因子家族成员4（）的溶瘤痘苗病毒（oVV-），并分别探讨了其在AML细胞中的抗肿瘤活性以及与阿糖胞苷联合使用时的抗肿瘤活性。
实验证实oVV能够高效且特异性地感染白血病细胞，并增强基因表达。流式细胞术和蛋白质免疫印迹表明oVV-可增强AML细胞的凋亡和G2/M期阻滞，并导致显著的癌细胞死亡。此外，还在体外和体内研究了oVV-与阿糖胞苷的协同效果；该联合用药在体外显著抑制白血病细胞的存活，在体内显著抑制移植的KG-1 AML肿瘤生长。
简而言之，oVV-可提高白血病细胞对阿糖胞苷的敏感性，并在体外和体内诱导细胞凋亡。因此，oVV-可能是一种有前景的白血病治疗候选药物，与阿糖胞苷联合使用代表了一种潜在的抗肿瘤治疗方法。
