A dual cancer-specific recombinant adenovirus suppresses the growth of liver cancer cells in vivo and in vitro

Anticancer Drugs. 2020 Feb;31(2):110-122. doi: 10.1097/CAD.0000000000000854.

Abstract

Oncolytic virus therapy is emerging as important means in cancer treatment. In a previous study, we constructed a dual cancer-specific antitumor recombinant adenovirus, designating it Ad-apoptin-hTERTp-E1a (Ad-VT). This study aimed to investigate the anticancer potential of recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) in liver cancer. Crystal Violet staining and CCK-8 assays were used to analyse the inhibitory effect of recombinant adenovirus on human hepatoma cell line QGY-7703 and SMMC-7721. Ad-VT had a significant tumour killing inhibitory effect on QGY-7703 and SMMC-7721 cells that was both dose and a time dependent. Ad-VT-induced apoptosis of QGY-7703 cells was detected using Hoechst, Annexin V, and JC-1 staining, as well as western blotting. Recombinant adenovirus had a strong apoptosis-inducing effect on QGY-7703 cells, and killed QGY-7703 cells mainly through the mitochondrial apoptotic pathway. QGY-7703 cells invasion were detected using cell-scratch and Transwell assays. Recombinant adenovirus could significantly inhibit the invasion of QGY-7703 cells over a short period of time. The pGL4.51 plasmid was used to transfect QGY-7703 cells to construct tumour cells stably expressing luciferase (QGY-7703-LUC). The tumour inhibition effect of Ad-VT in vivo was subsequently confirmed by establishing a tumour-bearing nude mouse model. Ad-VT could effectively inhibit tumour growth and prolong survival of the mice. Recombinant adenovirus Ad-VT has the characteristics of tumour-specific replication and specific tumour killing, and could inhibit the growth of liver cancer QGY-7703 cells and promote their apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Apoptosis
  • Cell Proliferation*
  • Female
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oncolytic Virotherapy / methods*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays