[Mechanism of DADS in the bystander effect of HSV-tk/GCV suicide gene therapy system in lens epithelial cells]

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Apr;36(4):329-34. doi: 10.3969/j.issn.1672-7347.2011.04.009.
[Article in Chinese]

Abstract

Objective: To investigate the mechanism and effect of diallyl disulfide (DADS) on the bystander effect of herpes simplex virus kinase/ganciclovir (HSV-tk/GCV) suicide gene therapy system which was mediated by recombinant adeno-associated virus (rAAV) in lens epithelial cells.

Methods: Immunohistochemistry method was used to determine the distribution of connexin 43 (Cx43) protein in cultured rabbit lens epithelial cells and rabbit lens epithelial cells transfected by HSV-tk suicide gene. Cx43 protein was measured and analyzed in cultured rabbit lens epithelial cells and rabbit lens epithelial cells transfected by HSV-tk suicide gene that was induced by various DADS. Cell survival was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.

Results: DADS increased the Cx43 protein expression in cultured rabbit lens epithelial cells and rabbit lens epithelial cells transfected by HSV-tk suicide gene, and especially in 50 μmol/L DADS. After combining with DADS, the bystander effect was significantly improved (P<0.05).

Conclusion: DADS can elevate the expression of Cx43 protein and enhance the bystander effect of HSV-tk/GCV suicide gene therapy system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Allyl Compounds / pharmacology*
  • Animals
  • Antiviral Agents / pharmacology
  • Bystander Effect / drug effects*
  • Cells, Cultured
  • Connexin 43 / metabolism
  • Disulfides / pharmacology*
  • Epithelial Cells / metabolism
  • Ganciclovir / pharmacology
  • Genes, Transgenic, Suicide*
  • Lens, Crystalline / cytology
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Plant Oils
  • Rabbits
  • Simplexvirus / enzymology*
  • Thymidine Kinase / genetics*
  • Thymidine Kinase / metabolism

Substances

  • Allyl Compounds
  • Antiviral Agents
  • Connexin 43
  • Disulfides
  • Plant Oils
  • diallyl disulfide
  • Thymidine Kinase
  • Ganciclovir