[Suicide gene therapy for glioma using HSV-tk/GCV system]

To establish a suicide gene therapy system HSV-tk/GCV for glioma treatment in vitro as well as in vivo and test its efficacy.

C6 rat glioma cells were infected with recombinant retrovirus containing HSV-tk gene. Following selection the C6/tk cell line which stably expressed tk was cloned. The sensitivities of C6/tk cells to several nucleoside analogues, such as GCV, BVdU, ACV, were compaired by the growth inhibition studies. Antitumor effects were also observed after GCV treatment in nude mice bearing tumors derived from C6/tk cells.

The growth inhibition studies showed that GCV was the most efficient prodrug, and C6/tk cells were highly sensitive to GCV, with an IC50 < 0.2 mumol/L, being 500-fold less than that in tk-negative C6 cells. In vivo studies showed similar results. Significant tumor inhibition was found in the treatment group.

Tumor cells expressing HSV-tk gene can be eradicated by administration of GCV in vitro as well as in vivo.