In vivo antitumor effect of cationic liposomes containing diphtheria toxin A-chain gene on cells infected with bovine leukemia virus.
A plasmid pLTR-DT which contained a gene for diphtheria toxin A-chain (DT-A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) (BLV-LTR) in the multicloning site of pUC-18 was entrapped in cationic liposomes composed of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride (TMAG), dioleoyl phosphatidylethanolamine (DOPE) and dilauroyl phosphatidylcholine (DLPC) (1:2:2, molar ratio) (TMAG-liposome), and their antitumor effect on BLV-infected tumor cells was examined in vivo. The cationic TMAG-liposome containing pLTR-DT was successively injected into the tumor transplanted to nude mice. The growth of tumor was significantly inhibited by the injection of cationic TMAG-liposome containing pLTR-DT. On the other hand, TMAG-liposome containing pUC18 plasmids showed no such effect. These results suggest that a DT-A expression plasmid under the control of BLV-LTR is highly toxic to the BLV-infected tumor cells, and that the cationic liposomes, such as TMAG-liposome, may be efficient transfection reagent for BLV-infected tumor cells and can be utilized for DT-A gene delivery into BLV-infected tumor cells in vivo.
Tana
Department of Cell Chemistry, Institute of Cellular and Molecular Biology, Okayama University Medical School, Japan.
Watarai
S
S
Lee
J T
JT
Onuma
M
M
Ochiai
K
K
Kakidani
H
H
Yasuda
T
T
D000818:Animals; D000970:Antineoplastic Agents; D002417:Cattle; D002478:Cells, Cultured; D004167:Diphtheria Toxin / Q000096:biosynthesis* / Q000235:genetics; D004337:Drug Carriers; D016583:Enzootic Bovine Leukosis / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005971:Glutamates; D007668:Kidney; D001909:Leukemia Virus, Bovine / Q000235:genetics*; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010957:Plasmids; D011994:Recombinant Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D012756:Sheep; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D004337:Drug Carriers; D005971:Glutamates; D008081:Liposomes; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; C029795:diphtheria toxin fragment A; C084512:didodecyl N-(alpha-trimethylammonioacetyl)glutamate; C015153:1,2-dilauroylphosphatidylcholine; C020888:1,2-dielaidoylphosphatidylethanolamine