J Korean Pediatr Soc.  2003 Jun;46(6):541-547.

Novel Gap Junction Molecules, Connexin 37, Enhances the Bystander Effect in HSVtk/GCV Gene Therapy

• Kim SY
• Yi HK
• Lee JC
• Hwang DJ
• Hwang PH
• Lee DY
• Cho SC

Abstract

PURPOSE
Gap junction intercellular communication(GJIC) is an important mechanism of the bystander effect in herpes simplex thymidine kinase/ganciclovir(HSVtk/GCV) gene therapy Therefore, we attempted to enhance the bystander effect in vitro by exogenous overexpressing connexin 37(Cx37) in cells to increase GJIC.
METHODS
NIH3T3 cells were transfected with the Cx37 and HSVtk gene or the HSVtk gene alone by the calcium phosphate method, and we detected their expression from these cells by RT-PCR. GCV-mediated cytotoxicity and the bystander effect of each transfectant was then assessed and compared.
RESULTS
Cells transfected with HSVtk became sensitive to low concentration of GCV. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx37 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene in vitro. Co-expression of the HSVtk and Cx37 genes potentiates HSVtk/GCV gene therapy through the bystander effect.
CONCLUSION
These results indicated that the increase of GJIC using Cx37 have potentiated the by stander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.

Keyword

Connexin 37; HSVtk/GCV; Gene therapy

MeSH Terms

Bystander Effect*
Calcium
Gap Junctions*
Genes, Neoplasm
Genetic Therapy*
Herpes Simplex
Thymidine
Calcium
Thymidine