Factors influencing the drug sensitization of human tumor cells for in situ lipofection.
The cisplatin induced enhancement of in situ lipofection was optimized by considering the factors that can increase the degree of sensitization. Two other anticancer drugs, mechlorethamine (nitrogen mustard) and taxol, enhanced CAT gene expression but the degree of sensitization was not as great as cisplatin. Besides human 2008 ovarian cancer cells we also found that human lung (A549) and head and neck cancer cells (SCC 25) were transiently sensitized by cisplatin. The transfectability of the two commercially available cationic liposomes, Lipofectin and LipofectAmine, was either weak or not consistent among tumors tested. In vivo transfection efficiency of 2008 cells was the highest at 1 microgram DNA per nmol or microgram liposome with all three cationic liposomes. In vitro transfection efficiency of 2008 cells at 1:1 (microgram of DNA:nmole of DC-chol/DOPE liposome) increased in a dose-dependent manner while at 1:10, an optimal ratio for in vitro lipofection, rapidly decreased with an increase in dose. This result indicated that there was a correlation between in vivo and in vitro lipofection at 1:1 ratio for delivering liposomal DNA. Most of the DNA injected into the tumor was concentrated in the tumor and in the skin above the tumor whether cisplatin was preinjected or liposomes were used as carriers.
Son
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K
Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15261, USA.
Huang
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D002411:Cation Exchange Resins / Q000737:chemistry*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002784:Cholesterol / Q000031:analogs & derivatives; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy; D008466:Mechlorethamine / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D014162:Transfection
D000970:Antineoplastic Agents; D002411:Cation Exchange Resins; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D010714:Phosphatidylethanolamines; D001761:Bleomycin; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D008466:Mechlorethamine; C020888:1,2-dielaidoylphosphatidylethanolamine; D004247:DNA; D002784:Cholesterol; D015500:Chloramphenicol O-Acetyltransferase; D017239:Paclitaxel; D002945:Cisplatin