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

Journal of the Korean Pediatric Society 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 Kim, Ho Keun Yi, Jung Chang Lee, Dong Jin Hwang, Pyoung Han Hwang, Dae Yeol Lee, Soo Chul Cho
Department of Pediatrics, Chonbuk National University, Medical School, Jeonju, Korea
Herpes Simplex Virus thymidine Kinase/Ganciclovir 유전자 치료에서 새로운 간격결합분자 Connexin 37에 의한 방관자 효과의 증가
김선영, 이호근, 이정창, 황동진, 황평한, 이대열, 조수철
전북대학교 의과대학 소아과학교실
Soo Chul Cho, Email: chosc@moak.chonbuk.ac.kr
: 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.
: 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.
: 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.
: 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.
Key Words: Connexin 37, HSVtk/GCV, Gene therapy

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