Selective killing of lung cancer cells using carcinoembryonic antigen promoter and double suicide genes, thymidine kinase and cytosine deaminase (pCEA-TK/CD)

Cancer Lett. 2012 Mar;316(1):31-8. doi: 10.1016/j.canlet.2011.10.015. Epub 2011 Oct 30.

Abstract

The application of gene therapy in cancer treatment is limited by non-specific targeting. In the present study, we constructed a recombinant plasmid, containing a carcinoembryonic antigen (CEA) promoter and double suicide genes thymidine kinase (TK) and cytosine deaminase (CD), henceforth referred to as pCEA-TK/CD. Our results showed that the CEA promoter can specifically drive target gene expression in CEA-positive lung cancer cells. In the presence of prodrugs 5-flucytosine and ganciclovir, pCEA-TK/CD transfection decreased inhibitory concentration 50 and increased apoptosis and cyclomorphosis. Our result suggests that gene therapy using pCEA-TK/CD may be a promising new approach for treating lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carcinoembryonic Antigen / genetics*
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cytosine Deaminase / biosynthesis
  • Cytosine Deaminase / genetics*
  • Cytosine Deaminase / metabolism
  • Flucytosine / pharmacology
  • Ganciclovir / pharmacology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Genes, Transgenic, Suicide*
  • Genetic Therapy / methods
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / therapy*
  • Plasmids / genetics
  • Prodrugs / pharmacokinetics
  • Prodrugs / pharmacology
  • Promoter Regions, Genetic
  • Thymidine Kinase / biosynthesis
  • Thymidine Kinase / genetics*
  • Thymidine Kinase / metabolism
  • Transfection / methods

Substances

  • Carcinoembryonic Antigen
  • Prodrugs
  • Flucytosine
  • Thymidine Kinase
  • Cytosine Deaminase
  • Ganciclovir