Killing effect of TNF-mediated by conditionally replicating adenovirus on esophageal cancer and lung cancer cell lines

Int J Clin Exp Pathol. 2015 Nov 1;8(11):13785-94. eCollection 2015.

Abstract

Objective: The killing effect of TNF mediated by conditionally replicating adenovirus SG502 on human cancer cell lines was assessed by in vivo and in vitro experiments.

Methods: The recombinant adenovirus SG502-TNF was used to infect human lung cancer cell line A549 and human esophageal cancer cell line TE-1. The expression of the exogenous gene and its inhibitory effect on the tumor cell lines were thus detected. Tumor transplantation experiment was performed in mice with the purpose of assessing the inhibitory effect of the adenovirus on tumor cells and tumor formation. The targeting of the adenovirus and the mechanism of tumor inhibition were discussed by in vivo imaging technology, HE staining and TUNEL assay.

Results: Recombinant adenovirus SG502-TNF targeted the tumor cells specifically with stable expression of TNF, which produced a killing effect on tumor cells by regulating the apoptotic signaling pathway.

Conclusion: Recombinant adenovirus SG502-TNF possessed significant killing effect on TE-1 cells either in vivo or in vitro. This finding demonstrated the potential clinical application of adenovirus SG502.

Keywords: Adenovirus; cancer cells; tumor necrosis factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / growth & development*
  • Adenoviridae / metabolism
  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Esophageal Neoplasms / virology
  • Feasibility Studies
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Genetic Therapy / methods*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Lung Neoplasms / virology
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / genetics
  • Oncolytic Viruses / growth & development*
  • Oncolytic Viruses / metabolism
  • Telomerase / biosynthesis
  • Telomerase / genetics
  • Time Factors
  • Tumor Burden
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Virus Replication*
  • Xenograft Model Antitumor Assays

Substances

  • Tumor Necrosis Factor-alpha
  • TERT protein, human
  • Telomerase