The use of cationic liposomes DC-CHOL/DOPE and DDAB/DOPE for direct transfer of Escherichia coli cytosine deaminase gene into growing melanoma tumors.
An attempt was made to use simple cationic liposomes DC-Chol/DOPE and DDAB/DOPE (DC-Chol is 3 beta (N(N',N-dimethylaminoethane) carbamoyl) cholesterol, DDAB is dimethyldioctadecyl ammonium bromide and DOPE is dioleoylphosphatidylethanolamine) for transfer of Escherichia coli cytosine deaminase 'suicide' gene under the control of tissue-specific tyrosinase gene promoter directly into the murine melanoma B16(F10) tumor. Several repeated intratumoral injections of DNA-liposome complexes followed by intraperitoneal administrations of 5-fluorocytosine, which is converted to 5-fluorouracil, caused strong retardation of murine melanoma B16(F10) tumor growth and, in some cases, rejection of the pre-established tumor. The inhibition of tumor growth expressed as the increased survival of mice is better seen in the case of using DNA-DDAB/DOPE complexes as compared to DNA-DC-Chol/DOPE ones. It seems that the observed therapeutic effect appears to result from several factors: 5-fluorouracil generation by transfected cells, liposome toxicity (DDAB is more toxic than DC-Chol and hence more tumor cells are killed), increased transfection efficiency of surviving cancer cells (in this case DDAB is a better transfection agent than DC-Chol) and, finally, the bystander effect which causes destruction of cells untransfected with CD gene by easily diffusible 5-fluorouracil.
Szala
S
S
Department of Tumor Biology, Institute of Oncology, Gliwice, Poland.
Missol
E
E
Sochanik
A
A
Strozyk
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002412:Cations; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D043525:Cytosine Deaminase; D004337:Drug Carriers; D004926:Escherichia coli / Q000201:enzymology*; D005472:Fluorouracil / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D008081:Liposomes; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy; D009700:Nucleoside Deaminases / Q000235:genetics*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*
D000964:Antimetabolites, Antineoplastic; D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C046112:didodecyldimethylammonium; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; C020888:1,2-dielaidoylphosphatidylethanolamine; D002784:Cholesterol; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D005472:Fluorouracil