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BioMed Research International
Volume 2014 (2014), Article ID 156356, 9 pages
http://dx.doi.org/10.1155/2014/156356
Research Article

Durable Expression of Minicircle DNA-Liposome-Delivered Androgen Receptor cDNA in Mice with Hepatocellular Carcinoma

1Sex Hormone Research Center, Center for Molecular Medicine, and Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan
2Graduate Institution of Clinical Medical Science, Department of Medicine, School of Medicine, China Medical University, Taichung 404, Taiwan
3Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA

Received 4 September 2013; Revised 25 December 2013; Accepted 21 January 2014; Published 6 March 2014

Academic Editor: Guillermo Mazzolini

Copyright © 2014 Tian-You Chang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. The most common gene-based cancer therapies involve the suppression of oncogenic molecules and enhancement of the expression of tumor-suppressor genes. Studies in noncancer disease animal models have shown that minicircle (MC) DNA vectors are easy to deliver and that the proteins from said MC-carrying DNA vectors are expressed over a long period of time. However, delivery of therapeutic genes via a liposome-mediated, MC DNA complex has never been tested in vascular-rich hepatocellular carcinoma (HCC). Liposome-mediated DNA delivery exhibits high in vivo transfection efficiency and minimal systemic immune response, thereby allowing for repetitive interventions. In this study, we evaluated the efficacy of delivering an MC-liposome vector containing a 3.2 kb androgen receptor (AR; HCC metastasis suppressor) cDNA into Hepatitis B Virus- (HBV-) induced HCC mouse livers. Results. Protein expression and promoter luciferase assays revealed that liposome-encapsulated MC-AR resulted in abundant functional expression of AR protein (100 kD) for up to two weeks. The AR cDNA was also successfully delivered into normal livers and diseased livers, where it was persistently expressed. In both normal livers and livers with tumors, the expression of AR was detectable for up to 60 days. Conclusion. Our results show that an MC/liposome delivery system might improve the efficacy of gene therapy in patients with HCC.