Adenovirus armed with VGLL4 selectively kills hepatocellular carcinoma with G2/M phase arrest and apoptosis promotion

Biochem Biophys Res Commun. 2018 Sep 18;503(4):2758-2763. doi: 10.1016/j.bbrc.2018.08.036. Epub 2018 Aug 16.

Abstract

The Vestigial-Like Family Member 4 (VGLL4) functions as a native inhibitor of cell proliferation and tumor growth through multiple signaling pathways. We first discovered that VGLL4 causes G2/M phase arrest in hepatocellular carcinoma (HCC) cells. Then, we designed a novel survivin-regulated oncolytic adenovirus Ad-sp-VGLL4 carrying the VGLL4 gene. Ad-sp-VGLL4 exerted high HCC-targeting-selectivity but is less harmful to normal cells. This adenovirus construction enhanced antitumor activity due to G2/M phase arrest and enhanced apoptosis. It's also indicated that Ad-sp-VGLL4 could suppress the growth of transplanted tumor of HCC in vivo experiment. Taken together, our results suggest that Ad-sp-VGLL4 possesses strong antitumor capacity and has great potential use for HCC therapy.

Keywords: Apoptosis; G2/M phase arrest; Oncolytic adenovirus; Survivin promotor; VGLL4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Mice
  • Mice, Nude
  • Oncolytic Virotherapy / methods
  • Oncolytic Viruses / genetics*
  • Oncolytic Viruses / metabolism
  • Signal Transduction
  • Survivin / genetics
  • Survivin / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • BIRC5 protein, human
  • Survivin
  • Transcription Factors
  • VGLL4 protein, human