Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by transferrin receptor through trans-arterial delivery.

Abstract

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.

• Authors: Qin Lu, Gao-Jun Teng, Yue Zhang, Huan-Zhang Niu, Guang-Yu Zhu, Yan-Li An, Hui Yu, Guo-Zhao Li, Ding-Hong Qiu, Chuan-Ging Wu
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 7 Issue 2 Pg. 218-24 (Feb 2008) ISSN: 1555-8576 [Electronic] United States
• PMID: 18347429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Receptors, Transferrin
• Transferrin

Topics

• Animals
• Blotting, Western
• Carcinoma, Hepatocellular (diagnostic imaging, pathology, therapy)
• Cell Line, Tumor
• Fluorescent Antibody Technique, Indirect
• Gene Transfer Techniques
• Genes, p53
• Genetic Therapy (methods)
• Humans
• Immunohistochemistry
• Liposomes
• Liver Neoplasms (diagnostic imaging, pathology, therapy)
• Radiography
• Receptors, Transferrin (metabolism)
• Survival Analysis
• Time Factors
• Transfection (methods)
• Transferrin (genetics)
• Transgenes
• Tumor Burden
• Xenograft Model Antitumor Assays (methods)