Objective: To study the characteristics of suicide gene system of the herpes simplex virus thymidine kinase (HSV-tk) gene in tumor cells and explore the apoptosis phenomena in this system and its effect on dendritic cells (DC).
Method: HSV-tk was transduced into the breast cancer cell line MCF-7 cells with a retrovirus vector. Apoptosis was examined by electro-microscopy and FACS. DCs were induced from cord blood CD(34)(+) cells with a combination of cytokines (GM-CSF, TNF-alpha, SCF and FL) and (3)H-TdR was adopted to determine the proliferation of T cells.
Results: In vitro experiment showed a dose-dependent cell killing of the HSV-tk gene transducted cells on ganciclovir (GCV) treatment. The apoptosis rate increased to 31.3% from the control group of 19.3%. Apoptosis is the important mechanism in bystander effect of HSV-tk/GCV system. The CD(1a)(+) and HLA-DR(+) cells in the induced DC were of (27.18 +/-1.56)% and (93.7 +/- 1.0)%, respectively. Co-incubation of DC with apoptotic cells further stimulated the proliferation of T cells.
Conclusion: It suggested that HSV-tk/GCV system, alone or combined with radiotherapy, be a promising suicide gene therapy for cancer patient and an approach to enhancing DC function.