Antitumor effect of COOH-terminal polypeptide of human TERT is associated with the declined expression of hTERT and NF-κB p65 in HeLa cells

Oncol Rep. 2015 Dec;34(6):2909-16. doi: 10.3892/or.2015.4298. Epub 2015 Sep 21.

Abstract

Human telomerase reverse transcriptase (hTERT) plays an important role in the development of tumors and has been investigated as a potent target for anticancer therapy. In the present study, we constructed a recombinant adenovirus, Ad-EGFP-C197 which was capable of expressing COOH‑terminal polypeptide of hTERT (amino acid 936-1,132, termed as C197 for the reason that it contains 197 amino acids). Infection of HeLa cells with Ad-EGFP-C197 suppressed the activity of telomerase, decreased the expression of hTERT and NF-κB p65, and induced rapid growth delay and apoptosis of HeLa cells in vitro. In nude mice xenografted with HeLa tumors, injection of Ad-EGFP-C197 into the tumor nodule significantly slowed tumor growth and promoted tumor cell apoptosis, as well as reduced the expression of NF-κB p65 in tumor tissues. In the present study, we suggest that the antitumor effect of C197 is associated with the declined expression of hTERT and NF-κB p65. Our results highlight the potential of C197 in tumor therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Therapy
  • HeLa Cells
  • Humans
  • Mice
  • Peptides / genetics*
  • Promoter Regions, Genetic
  • Telomerase / biosynthesis*
  • Telomerase / genetics
  • Transcription Factor RelA / biosynthesis*
  • Transcription Factor RelA / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy
  • Xenograft Model Antitumor Assays

Substances

  • DNA-Binding Proteins
  • Peptides
  • Transcription Factor RelA
  • TERT protein, human
  • Telomerase