Oncolytic adenovirus encoding tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits the growth and metastasis of triple-negative breast cancer

Cancer Biol Ther. 2013 Nov;14(11):1016-23. doi: 10.4161/cbt.26043. Epub 2013 Aug 28.

Abstract

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising cancer therapeutic target due to its selective apoptosis-inducing effect in cancer cells. To efficiently deliver TRAIL to the tumor cells, an oncolytic adenovirus (p55-hTERT-HRE-TRAIL) carrying the TRAIL coding sequence was constructed. In the present study, we aimed to investigate the effect of p55-hTERT-HRE-TRAIL on the growth and metastasis of triple-negative breast cancer (TNBC). We observed that infection of the recombinant adenovirus resulted in expression of TRAIL and massive cell death in a TNBC cell line MDA-MB-231. This effect is much weaker in MCF-10A, which is a normal breast cell line. Administration of P55-HTERT-HRE-TRAIL significantly reduced orthotopic breast tumor growth and extended survival in a metastatic model. Our results suggest the oncolytic adenovirus armed with P55-HTERT-HRE-TRAIL, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of TNBC.

Keywords: adenovirus; triple-negative breast cancer (TNBC); tumor necrosis factor-related apoptosis inducing ligand (TRAIL); virotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / physiology
  • Apoptosis*
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Ductal, Breast / therapy
  • Female
  • Humans
  • Neoplasm Metastasis
  • Oncolytic Virotherapy
  • Oncolytic Viruses / genetics*
  • Oncolytic Viruses / physiology
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Triple Negative Breast Neoplasms / pathology*
  • Triple Negative Breast Neoplasms / therapy

Substances

  • TNF-Related Apoptosis-Inducing Ligand