溶瘤病毒
胰腺癌
癌症研究
溶瘤腺病毒
医学
不可逆电穿孔
PI3K/AKT/mTOR通路
癌症
细胞凋亡
免疫原性细胞死亡
癌细胞
免疫系统
蛋白激酶B
电穿孔
生物
免疫学
内科学
肿瘤细胞
基因
生物化学
作者
Shuxin Sun,Yang Liu,Chaobin He,Wanming Hu,Wenfeng Liu,Xin Huang,Jiali Wu,Fengxiao Xie,Chen Chen,Jun Wang,Yongcheng Lin,Wenbo Zhu,Yan Gao,Jing Cai,Shengping Li
标识
DOI:10.1016/j.canlet.2020.12.018
摘要
NanoKnife, a nonthermal ablation technique also termed irreversible electroporation (IRE), has been adopted in locally advanced pancreatic cancer (LAPC) treatment. However, reversible electroporation (RE) caused by heterogeneous electric field magnitude leads to inadequate ablation and tumor recurrence. Alphavirus M1 has been identified as a novel natural oncolytic virus which is nonpathogenic and with high tumor selectivity. This study evaluated improvements to therapeutic efficacy through combination therapy incorporating NanoKnife and M1 virus. We showed that IRE triggered reactive oxygen species (ROS)-dependent apoptosis in pancreatic cancer cells (PCCs) mediated by phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway suppression. When NanoKnife was combined with M1 virus, the therapeutic efficacy was synergistically enhanced. The combinatorial treatment further inhibited tumor proliferation and prolonged the survival of orthotopic pancreatic cancer (PC)-bearing immunocompetent mice. In depth, NanoKnife enhanced the oncolytic effect of M1 by promoting its infection. The combination turned immune-silent tumors into immune-inflamed tumors characterized by T cell activation. Clinicopathologic analysis of specific M1 oncolytic biomarkers indicated the potential of the combination regimen. The combinatorial therapy represents a promising therapeutic efficacy and may ultimately improve the prognosis of patients with LAPC.
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