Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment

Background and Objectives: We studied antitumor effects and cell death induced by cationic liposome-mediated gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir treatment in cultured rat T9 glioma cells and in experimental gliomas produced from this cell line. Methods: To transfer genes we used small unilamellar cationic liposomes containing N-(alpha -trimethylammonioacetyl)-didodecyl-D-glutamate chloride. Video-enhanced contrast differential interference contrast microscopy was used for morphologic observations of cultured cells. Results: When we treated the cells or implanted gliomas with the liposomes and ganciclovir, a strong effect was seen against tumor cells. and survival of tumor-implanted rats was increased. Morphologically, cell death observed after HSV-tk gene/liposome and ganciclovir treatment in the cultured glioma cells included both apoptosis and necrosis. Conclusions: Introduction of the HSV-tk gene in a DNA-liposome complex followed by ganciclovir treatment induced both apoptosis and necrosis, which together resulted in a potent antitumor effect. J. Surg. Oncol. 2001:76:19-25. (C) 2001 Wiley-Liss, Inc.