[Adenoviral vector expressing the TRAIL gene driven by the hTERT promoter].
BACKGROUND
Resistance can be overcome by modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence. We constructed an adenoviral vector with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter (designated Ad/TRAIL-F/RGD), and evaluated its antitumor activity in vitro and in vivo.


METHODS
The induction of apoptosis by the new vector Ad/TRAIL-F/RGD was evaluated in human carcinoma cells derived from hepatocellular carcinoma (Hep G2, Hep 3b), pancreatic carcinoma (Panc-1, Capan-1), and colon carcinoma (LOVO, SW 620) . Cell viability was measured by the XTT assay and GFP expression and apoptosis induction by fluorescence-activated cell sorting (FACS) and Western blot. In vivo experiments were performed in an orthotopic pancreas tumor model in nu/nu nude mice.


RESULTS
Treatment with Ad/TRAIL-F/RGD and Ad/gTRAIL resulted in significantly reduced cell viability in comparison to PBS and Ad/CMV-GFP treatment in all examined human carcinoma cell lines. In addition, mice treated with Ad/TRAIL-F/RGD showed a significantly decreased tumor growth than both control groups.


CONCLUSIONS
Our results suggest that Ad/TRAIL-F/RGD may become a potent therapeutic agent for the treatment of different human solid carcinomas.
Jacob
D
D
Klinik für Transplantations-, Viszeral- und Allgemeinchirurgie, Charité Campus-Virchow, Humboldt-Universität zu Berlin, Deutschland. dietmar.jacob@charite.de
Davis
J
J
Schumacher
G
G
Bahra
M
M
Neuhaus
P
P
Fang
B
B
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor / Q000473:pathology*; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology*; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018014:Gene Transfer Techniques; D005809:Genes, Regulator / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000235:genetics*; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand; D019098:Telomerase / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C047981:arginyl-glycyl-aspartic acid; D019098:Telomerase