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Hepatobiliary Pancreat Dis Int ; 3(4): 552-7, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15567744

RESUMEN

BACKGROUND: It is widely recognized that the growth of solid tumor depends on angiogenesis. Vascular endothelia growth factor (VEGF) is an endothelial cell-specific mitogen that promotes angiogenesis in solid tumor. Inhibition of angiogenesis is considered a promising approach for cancer therapy, and treatments including administration of antisense drugs and RNA interference for the VEGF gene are geared to the suppression of tumor angiogenesis. METHODS: As a new approach for gene therapy of hepatocellular carcinoma (HCC), four groups of antisense oligodeoxynucleotide (ASODN) (A-Cap, A-AUG, A-UGA and A-Exon-3) were used to block the expression of VEGF, then VEGF mRNA and protein were detected by RT-PCR and Western blot. RESULTS: After treatment with ASODN, the relative VEGF mRNA levels of A-Cap, A-AUG, A-UGA, and A-Exon-3 were decreased significantly to (32+/-9)%, (63+/-1)%, (86+/-3)%, and (70+/-5)%, respectively(F=64.18, P<0.001). The relative VEGF protein levels of A-Cap, A-AUG, A-UGA and A-Exon-3 were decreased significantly to (41+/-5)%, (59+/-3)%, (88+/-7)%, and (79+/-9)% respectively (F=60.64, P<0.001). CONCLUSIONS: Among the four ASODNs, the ASODN for Cap structure showed the strongest inhibitory effect and that for A-UGA, the least (P<0.05 ). The inhibitory effect of ASODN on the expression of VEGF proteins was similar to that of VEGF mRNA expression.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Oligonucleótidos Antisentido/farmacología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética , Western Blotting , Carcinoma Hepatocelular/patología , Hipoxia de la Célula , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/patología , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
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