Abstract
A plasmid expressing the soluble tumor necrosis factor (TNF)-related apoptosis-inducing ligand, sTRAIL (amino acids 114-281 of TRAIL), driven by rat progression-elevated gene-3 (rPEG) promoter was constructed and evaluated. Transfection of embryonal carcinoma (EC) cells with the plasmid resulted in significant cellular apoptosis and elevated expression of death receptor 4 (DR4) and death receptor 5 (DR5). Direct intratumoral injection of DNA:liposome complexes suppressed tumor growth significantly and prolonged the survival of teratocarcinoma-bearing mice. Histological examination and serum analyses showed the absence of detectable toxicity in all examined tissues, including liver. Our results demonstrate that sTRAIL gene expression driven by the rPEG promoter may enable effective gene therapy against teratocarcinoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation / genetics*
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Apoptosis
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Cell Cycle Proteins / genetics*
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Cholesterol / administration & dosage
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DNA, Recombinant / administration & dosage
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DNA, Recombinant / genetics
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Drug Carriers
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Fatty Acids, Monounsaturated / administration & dosage
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Genetic Therapy*
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Humans
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Peptide Fragments / biosynthesis
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Peptide Fragments / genetics*
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Promoter Regions, Genetic / genetics*
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Protein Phosphatase 1
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Proto-Oncogene Proteins / genetics*
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Quaternary Ammonium Compounds / administration & dosage
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Rats
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Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis
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Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / therapeutic use
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Simian virus 40 / genetics
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Telomerase / genetics
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Teratocarcinoma / pathology
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Teratocarcinoma / therapy*
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Transfection
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Xenograft Model Antitumor Assays
Substances
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Antigens, Differentiation
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Cell Cycle Proteins
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DNA, Recombinant
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Drug Carriers
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Fatty Acids, Monounsaturated
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Peptide Fragments
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Ppp1r15a protein, rat
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Proto-Oncogene Proteins
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Quaternary Ammonium Compounds
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Recombinant Fusion Proteins
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soluble tumor necrosis factor-related apoptosis-inducing ligand (114-281), rat
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Cholesterol
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TERT protein, human
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Telomerase
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PPP1R15A protein, human
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Protein Phosphatase 1
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1,2-dioleoyloxy-3-(trimethylammonium)propane