High volume hydrodynamic injection of plasmid DNA via the hepatic artery results in a high level of gene expression in rat hepatocellular carcinoma induced by diethylnitrosamine
Article first published online: 16 JUN 2006
Copyright © 2006 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 8, Issue 8, pages 1018–1026, August 2006
How to Cite
Tada, M., Hatano, E., Taura, K., Nitta, T., Koizumi, N., Ikai, I. and Shimahara, Y. (2006), High volume hydrodynamic injection of plasmid DNA via the hepatic artery results in a high level of gene expression in rat hepatocellular carcinoma induced by diethylnitrosamine. J. Gene Med., 8: 1018–1026. doi: 10.1002/jgm.930
- Issue published online: 26 JUL 2006
- Article first published online: 16 JUN 2006
- Manuscript Accepted: 15 MAR 2006
- Manuscript Revised: 13 MAR 2006
- Manuscript Received: 16 JAN 2006
- hydrodynamic injection;
- naked plasmid DNA;
- hepatocellular carcinoma;
- gene therapy
Hydrodynamic injection of naked plasmid DNA (pDNA) via the tail vein is a safe and effective method of gene transfer to the liver. However, successful gene transfer has yet to be shown for hepatocellular carcinoma (HCC); therefore, we investigated the feasibility and efficacy of hydrodynamic injection via the tail vein and hepatic artery in a diethylnitrosamine (DEN)-induced HCC model in rats.
HCC was induced in Sprague-Dawley rats by 100 ppm DEN in drinking water. pCMV-SPORT-β-galactosidase (β-gal, 400 µg) was injected (i) via the tail vein in a volume of 0.1 ml/g in 30 s or (ii) via the hepatic artery in a volume of 5 or 10 ml at 1 ml/s, either with or without temporary occlusion of the inferior vena cava (IVC) and portal vein (PV). The liver was harvested 24 h after administration, and β-gal expression was evaluated with X-gal staining and measurement of enzymatic activity in tissue homogenates.
Hydrodynamic injection via the tail vein achieved transgene expression only in non-cancerous tissue (tumor: 0.16 ± 0.04%, non-tumor: 5.07 ± 1.66%). Hydrodynamic injection via the hepatic artery was tolerated, but failed to produce efficient transgene expression in tumor and non-tumor cells. On the other hand, concomitant use of temporary IVC/PV occlusion with hydrodynamic injection via the hepatic artery dramatically increased transgene expression in cancer cells, but tumor-selective gene transfer was not achieved with this procedure (tumor: 7.38 ± 3.66%, non-tumor: 7.77 ± 1.06%).
High-volume hydrodynamic injection of a pDNA solution via the hepatic artery with IVC/PV occlusion achieved a high level of gene expression in a HCC rat model. This gene transfer technique may have potential in clinical gene therapy for HCC. Copyright © 2006 John Wiley & Sons, Ltd.