Novel Gap Junction Molecules, Connexin 37, Enhances the Bystander Effect in HSVtk/GCV Gene Therapy .
- Author:
Sun Young KIM
;
Ho Keun YI
;
Jung Chang LEE
;
Dong Jin HWANG
;
Pyoung Han HWANG
;
Dae Yeol LEE
;
Soo Chul CHO
- Publication Type:In Vitro ; Original Article
- Keywords:
Connexin 37;
HSVtk/GCV;
Gene therapy
- MeSH:
Bystander Effect*;
Calcium;
Gap Junctions*;
Genes, Neoplasm;
Genetic Therapy*;
Herpes Simplex;
Thymidine
- From:Journal of the Korean Pediatric Society
2003;46(6):541-547
- CountryRepublic of Korea
- Language:Korean
-
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.
