Wang Biao, Yan Xu, Guo Qingguo, Li Yan, Zhang Haiyan, Xie Ji Sheng, Meng Xin
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences of China Medical University Shenyang, P.R. China.
Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang, P.R. China.
Oncotarget. 2015 Jun 30;6(18):16019-30. doi: 10.18632/oncotarget.3496.
The oncolytic measles virus Edmonston (MV-Edm) strain shows considerable oncolytic activity against a variety of human tumors. In this study, we report MV-Edm is able to trigger apoptosis pathways in infected tumor cells and elucidate the roles of cellular apoptosis in the whole oncolytic process. We also show that activated caspase 3, a key executioner of apoptosis, plays key roles in the oncolytic virotherapy. Activated caspase 3 can accelerate viral replication in cervical cancer cells and enhance the killing effects of the virus. Deficiency of caspase 3 either in tumor cells or in tumor xenograft significantly desensitized tumor to oncolysis with MV-Edm. In the infected cells, caspase 3 regulates interferon α release, which can inhibit viral replication in neighboring tumor cells. We propose that caspase-3 activation enhances the oncolytic effects of MV-Edm, thus inhibiting tumor growth in mice.
溶瘤性麻疹病毒埃德蒙斯顿（MV-Edm）毒株对多种人类肿瘤显示出相当大的溶瘤活性。在本研究中，我们报告MV-Edm能够在感染的肿瘤细胞中触发凋亡途径，并阐明细胞凋亡在整个溶瘤过程中的作用。我们还表明，活化的半胱天冬酶3（凋亡的关键执行者）在溶瘤病毒疗法中起关键作用。活化的半胱天冬酶3可加速病毒在宫颈癌细胞中的复制，并增强病毒的杀伤作用。肿瘤细胞或肿瘤异种移植中半胱天冬酶3的缺乏显著降低了肿瘤对MV-Edm溶瘤作用的敏感性。在感染的细胞中，半胱天冬酶3调节干扰素α的释放，这可以抑制邻近肿瘤细胞中的病毒复制。我们提出，半胱天冬酶-3的激活增强了MV-Edm的溶瘤作用，从而抑制小鼠肿瘤生长。
