title: Oncolytic vaccinia virus inhibits human hepatocellular carcinoma MHCC97-H cell proliferation via endoplasmic reticulum stress, autophagy and Wnt pathways.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China.|College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Jia
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Tianjin International Travel Health Care Center, Entry-Exit Inspection and Quarantine Bureau, Tianjin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou, China. med_bp@zju.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy / Q000821:virology; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D014616:Vaccinia virus / Q000235:genetics* / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D020598:Proto-Oncogene Proteins c-myb; D000077022:Survivin
keywords: Wnt signaling; autophagy; endoplasmic reticulum stress; gene therapy; hepatocellular carcinoma; oncolytic vaccinia virus