| Novel Gap Junction Molecules, Connexin 37, Enhances the Bystander Effect in HSVtk/GCV Gene Therapy |
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Sun Young Kim, Ho Keun Yi, Jung Chang Lee, Dong Jin Hwang, Pyoung Han Hwang, Dae Yeol Lee, Soo Chul Cho |
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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 |
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김선영, 이호근, 이정창, 황동진, 황평한, 이대열, 조수철 |
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전북대학교 의과대학 소아과학교실 |
Correspondence:
Soo Chul Cho, Email: chosc@moak.chonbuk.ac.kr
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| 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. |
| Key Words:
Connexin 37, HSVtk/GCV, Gene therapy |
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