Polyethylenimine-mediated suicide gene transfer induces a therapeutic effect for hepatocellular carcinoma in vivo by using an Epstein-Barr virus-based plasmid vector.

Abstract

The present study aimed to establish a novel efficient nonviral strategy for suicide gene transfer in hepatocellular carcinoma (HCC) in vivo. We employed branched polyethylenimine (PEI) and combined it with Epstein-Barr virus (EBV)-based plasmid vectors. The HCC cells transfected with an EBV-based plasmid carrying the herpes simplex virus-1 thymidine kinase (HSV-1 Tk) gene (pSES.Tk) showed up to 30-fold higher susceptibilities to ganciclovir (GCV) than those transfected with a conventional plasmid vector carrying the HSV-1 Tk gene (pS.Tk). The therapeutic effect in vivo was tested by intratumoral injection of the plasmids into HuH-7 hepatomas transplanted into C.B-17 scid/scid mutant (SCID) mice and subsequent GCV administrations. Treatment with pSES.Tk, but not pS.Tk, markedly suppressed growth of hepatomas in vivo, resulting in a significantly prolonged survival period of the mice. These findings suggest that PEI-mediated gene transfer system can confer efficient expression of the suicide gene in HCC cells in vivo by using EBV-based plasmid vectors.

• Authors: Masaki Iwai, Yoshinori Harada, Saiyu Tanaka, Akira Muramatsu, Takahiro Mori, Kei Kashima, Jiro Imanishi, Osam Mazda
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 291 Issue 1 Pg. 48-54 (Feb 15 2002) ISSN: 0006-291X [Print] United States
• PMID: 11829460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2002 Elsevier Science (USA).

Chemical References

• Polyethyleneimine
• Thymidine Kinase
• Ganciclovir

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Ganciclovir (administration & dosage)
• Gene Transfer, Horizontal
• Genetic Therapy (methods)
• Genetic Vectors (administration & dosage, chemistry, metabolism)
• Herpesvirus 1, Human (enzymology, genetics)
• Herpesvirus 4, Human (genetics)
• Humans
• Liver Neoplasms, Experimental (genetics, pathology, therapy)
• Mice
• Mice, SCID
• Neoplasm Transplantation
• Polyethyleneimine (administration & dosage, chemistry)
• Survival Rate
• Thymidine Kinase (administration & dosage, biosynthesis, genetics)
• Transfection
• Treatment Outcome
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays