Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer

J Exp Clin Cancer Res. 2010 Jul 13;29(1):94. doi: 10.1186/1756-9966-29-94.

Abstract

Background/aim: To explore the therapeutic effects of thymidine kinase (TK) expressed by enhanced vector pGL3-basic- hTERTp-TK-EGFP-CMV driven by human telomerase reverse transcriptase promoter (hTERTp) as well as cytomegalovirus immediate early promoter enhancer (CMV).

Materials/methods: Enhanced TK-EGFP expression was confirmed by fluorescent microscopy, real time PCR and telomerase activity. Its effects were examined by survival of tumor cells NPC 5-8F and MCF-7, index of xenograft implanted in nude mice and histology.

Results: Compared with non-enhanced vector pGL3-basic-TK-hTERTp-EGFP, TK expressed by the enhanced vector significantly decreased NPC 5-8F and MCF-7 cell survival rates after ganciclovir (GCV) treatment (p < 0.001) and tumor progress in nude mice with NPC xenograft and treated with GCV, without obvious toxicity to mouse liver and kidney.

Conclusion: The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy
  • Cell Proliferation
  • Cells, Cultured
  • Cytomegalovirus / genetics*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Enhancer Elements, Genetic / genetics*
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nasopharyngeal Neoplasms / enzymology
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / therapy*
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • Regulatory Sequences, Nucleic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase / genetics*
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism*

Substances

  • RNA, Messenger
  • Thymidine Kinase
  • TERT protein, human
  • Telomerase