Lipofectin enhances cellular uptake of antisense DNA while inhibiting tumor cell growth.
A natural DNA oligomer (15-mer) was synthesized with a sequence complementary to the translation initiation codon region of the human TGF-alpha mRNA and mixed with Lipofectin to form unilamellar complexes. It was found that tumor cell growth was inhibited when HCT116 cells were treated with Lipofectin-DNA oligomer complexes or with Lipofectin alone. Uptake of 32P-labeled 15-mers into colon tumor cells was compared in the presence and absence of Lipofectin. The amount of labeled oligomer found in cells that received optimal ratios of Lipofectin to DNA was 4- to 10-fold higher than the amount found in cells that received 32P-labeled DNA alone. Although Lipofectin-antisense DNA oligomer treatment of HCT116 cells caused a dose-dependent inhibition of cell growth, there was a subsequent rise in target mRNA product. Because the mechanism of growth inhibition could not involve an inhibition of TGF-alpha expression, it was concluded that Lipofectin probably exerts a nonspecific, detergent-like effect upon the cell membrane, producing an enhancement of TGF-alpha processing and release.
Yeoman
L C
LC
Department of Pharmacology, Baylor College of Medicine, Houston, Texas.
Danels
Y J
YJ
Lynch
M J
MJ
D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms; D016373:DNA, Antisense / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D007328:Insulin; D016376:Oligonucleotides, Antisense; D010714:Phosphatidylethanolamines; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; C020888:1,2-dielaidoylphosphatidylethanolamine; D015500:Chloramphenicol O-Acetyltransferase