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‐(α‐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. © 2001 Wiley‐Liss, Inc.