Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment.
OBJECTIVE
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.
Department of Neurosurgery, Nagoya University, Graduate School of Medicine, Nagoya, Japan.
T
T
Yoshida
M
M
Mizuno
K
K
Taniguchi
N
N
Nakayashiki
T
T
Wakabayashi
J
J
Yoshida
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002412:Cations; D016923:Cell Death; D015774:Ganciclovir / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D008081:Liposomes; D008857:Microscopy, Interference; D051381:Rats; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D002412:Cations; D008081:Liposomes; D013937:Thymidine Kinase; D015774:Ganciclovir