Another mechanism causing the bystander effect besides the gap junction's role during the glioma gene therapy with HSV-TK/GCV system.

Abstract

Human gene therapy has progressed from speculation to reality in the last several decades, and it has also been exploited in the field of the glioma treating. Due to the glioma having multiple varied genetic mutations, the antisense or target gene replacement are not so feasible for the treatment of these malignant tumors, that a novel approach named ‘suicide gene strategy’ has been performed. This method involves the transfer of the herpes simplex virus thymidine kinase (HSV-TK), whose production is capable of converting non-toxic prodrug—ganciclovir (GCV) to toxic metabolism, phosphated GCV, so the target tissue would be susceptible to destruction through the activation of the prodrug1–3. During this treatment of the glioma, a phenomenon named ‘bystander effect’ has been paid much attention, this is beacause GCV induced cytotoxicity is not only to the HSV-TK positive tumor cells, but also to the HSV-TK negative cells4,5. Although considerable attention has been directed toward the elucidating the mechanism underlying the bystander effect, little is known about how bystander cells can be rendered susceptible to GCV. In this study, we attempted to determine the possible mechanism of the bystander effect. We employed rat glioma cell line A15A5, which is TK-negative, and TF10.2, which were A15A5 cells transfected with TK gene. Another cell line we used is the C6 cell line, and C6-TF-PEGFP which were C6 transfected with PEGFP(Enhanced Green fluorescence protein).