All issues > Volume 46(6); 2003

Original Article

J Korean Pediatr Soc. 2003;46(6):541-547. Published online June 15, 2003.

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

Sun Young SY Kim¹, Ho Keun HK Yi¹, Jung Chang JC Lee¹, Dong Jin DJ Hwang¹, Pyoung Han PH Hwang¹, Dae Yeol DY Lee¹, Soo Chul SC Cho¹

¹Department of Pediatrics, Chonbuk National University, Medical School, Jeonju, Korea

Correspondence Soo Chul SC Cho ,Email: chosc@moak.chonbuk.ac.kr

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 bystander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.

Keywords :Connexin 37, HSVtk/GCV, Gene therapy