Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by transferrin receptor through trans-arterial delivery.
Cancer Biol Ther
; 7(2): 218-24, 2008 Feb.
Article
en En
| MEDLINE
| ID: mdl-18347429
Transferrin-DNA complex mediated by transferrin receptor in combination with interventional trans-arterial injection into a target organ may be a duel-target-oriented delivery means to achieve an efficient gene therapy. In this study, transferrin receptor expression in normal human hepatocyte and two hepatocellular-carcinoma cells (Huh7/SK-Hep1) was determined. p53-LipofectAMINE with different amounts of transferrin was transfected into the cells and the gene transfection efficiency was evaluated. After VX2 rabbit hepatocarcinoma model was established, the transferrin-p53-LipofectAMINE complex was delivered into the hepatic artery via interventional techniques to analyze the therapeutic p53 gene transfer efficiency in vivo by Western blot, immunohistochemical/immunofluorescence staining analysis and survival time. The results were transferrin receptor expression in Huh7 and SK-Hep1 cells was higher than in normal hepatocyte. Transfection efficiency of p53 was increased in vitro in both Huh7 and SK-Hep1 cells with increasing transferrin in a dose-dependent manner. As compared to intravenous administration, interventional injection of p53-gene complex into hepatic tumor mediated by transferrin-receptor, could enhance the gene transfer efficiency in vivo as evaluated by Western blot, immunohistochemical/immunofluorenscence staining analyses and improved animal survival (H = 12.567, p = 0.0019). These findings show the transferrin-transferrin receptor system combined with interventional techniques enhanced p53-gene transfer to hepatic tumor and the duel-target-oriented gene delivery may be an effective approach for gene therapy.
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Banco de datos:
MEDLINE
Asunto principal:
Receptores de Transferrina
/
Transfección
/
Genes p53
/
Técnicas de Transferencia de Gen
/
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Biol Ther
Asunto de la revista:
NEOPLASIAS
/
TERAPEUTICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
China