Increased Thymidine Kinase Activity and in vitro Bystander Effect by Double Transfer of HSVtk Gene into T98G Tumor Cells.
- Author:
Young Gyu KIM
1
Author Information
1. Department of Neurosurgery, College of Medicine, Chungbuk National University, Chungbuk, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Herpes simplex virus thymidine kinase;
Gene therapy;
Ganciclovir;
Bystander effect
- MeSH:
Bystander Effect*;
Cell Line;
Ganciclovir;
Genetic Therapy;
Simplexvirus;
Thymidine Kinase*;
Thymidine*
- From:Journal of Korean Neurosurgical Society
1999;28(3):293-299
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Transduction of retroviral-mediated herpes simplex virus thymidine kinase(HSVtk) gene into tumor cells and subsequent ganciclovir(GCV) treatment have been used as an experimental and clinical therapeutic strategy. Because non-transduced tumor cells can be killed by small proportion of transduced cells, known as bystander effect. Increasing bystander effect is useful strategy of suicidal gene therapy using HSVtk gene. To get a better bystander effect, we transduced T98G gliobastoma cells with HSVtk gene, single and double transduction with different marker genes respectively. Double HSVtk gene transduced cell lines showed significantly increased HSVtk activity(83%) by measuring the intracellular amount of phosphrylated 3H-GCV comparing to the single HSVtk gene transduced cell lines. In vitro bystander effect, examined by coculturing with HSVtk gene transduced cells and HSVtk- negative pa rental cells, was significantly increased on double HSVtk gene transduced cell lines. These results suggest that increasing herpes simplex virus thymidine kinase activity by double transfer of HSVtk gene into tumor cells can be a useful strategy for treating cancer with suicidal gene therapy.