[Targeted killing of colorectal tumor cells by lentiviral constructs containing CD/TK suicide genes and KDR promoter]

Nan Fang Yi Ke Da Xue Xue Bao. 2007 May;27(5):624-7.
[Article in Chinese]

Abstract

Objective: To investigate the selective killing of colorectal tumor cells by lentivirus-mediated double suicide gene under the regulation of KDR promoter.

Methods: 293T packaging cells were transfected with the plasmid FGW-KDRP-CD/TK to obtain the infectious viruses. KDR-expressing LoVo cells and LS174T cells that did not produce KDR were transfected with the recombinant virus, and the transfection efficiency was evaluated by the fluorecence microscope. RT-PCR was employed to examine the expression of CDglyTK. After treatment of the cells with 5-FC and GCV, the killing effects on the two cell lines were evaluated.

Results: The recombinant construct showed similar infection rate of the two cell lines. RT-PCR demonstrated that CDglyTK gene was expressed only in LoVo cells infected with FGW-KDRP-CD/TK but not in LS147T cells, and the sensitivity of the two cell lines to the prodrugs was significantly different (P<0.001). The killing effect of the double suicide gene was much stronger than that of single suicide gene administered (P<0.001).

Conclusion: The double suicide gene driven by KDR promoter has specific killing effect on the KDR-expressing colorectal tumor cells.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites / pharmacology
  • Apoptosis / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Cytosine Deaminase / genetics
  • Cytosine Deaminase / metabolism*
  • Flow Cytometry
  • Flucytosine / pharmacology
  • Ganciclovir / pharmacology
  • Genes, Transgenic, Suicide / genetics*
  • Genetic Vectors / genetics
  • Humans
  • Lentivirus / genetics
  • Promoter Regions, Genetic / genetics*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism*
  • Transfection
  • Vascular Endothelial Growth Factor Receptor-2 / genetics

Substances

  • Antimetabolites
  • Recombinant Fusion Proteins
  • Flucytosine
  • Thymidine Kinase
  • Vascular Endothelial Growth Factor Receptor-2
  • Cytosine Deaminase
  • Ganciclovir