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Oncolytic vaccinia virus inhibits human hepatocellular carcinoma MHCC97‐H cell proliferation via endoplasmic reticulum stress, autophagy and Wnt pathways
Author(s) -
Jia Xiaoyuan,
Chen Yongyi,
Zhao Xin,
Lv Chunwei,
Yan Jie
Publication year - 2016
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.2893
Subject(s) - oncolytic virus , survivin , autophagy , cancer research , biology , programmed cell death , wnt signaling pathway , apoptosis , endoplasmic reticulum , cell growth , signal transduction , microbiology and biotechnology , biochemistry , genetics , tumor cells
Background Hepatocellular carcinoma (HCC) is a highly lethal malignancy. Vaccinia virus (VV) possessed many inherent advantages with respect to being engineered as a vector for cancer gene therapy, although the mechanism of action remains to be explored further. Methods We constructed a thymidine kinase gene insertional inactivated VV, named VV‐Onco, and then tested its effects on cell viability, apoptosis and colony formation ability in a highly metastatic human hepatocellular carcinoma cell line MHCC97‐H, and also investigated the potential cell signal pathways involved in this action. Results VV‐Onco induced strong cytotoxicity and apoptosis and also inhibited the colony formation of MHCC97‐H cells. The tumor cell apoptosis induced by VV‐Onco is likely mediated via endoplasmic reticulum stress, autophagy and Wnt signaling pathways. The downregulation of survivin and c‐Myc may also play a role in VV‐Onco induced cell death. Conclusions The results of the present study provide new insights into the mechanisms of VV‐induced tumor cell death. The engineered recombinant VV containing optimized therapeutic transgenes may represent a new avenue for cancer gene therapy. Copyright © 2016 John Wiley & Sons, Ltd.