Abstract
Background/Aims
Gene therapy is a promising approach for treatment of hepatocellular carcinoma (HCC).
However, transduction of non-tumoral hepatocytes may lead to severe hepatitis when
using suicide gene therapy approaches. The aim of our study was to evaluate the gene
transfer efficiency into HCC cells and normal hepatocytes using human immunodeficiency
virus (HIV)-derived lentiviral vectors in vitro and in vivo.
Methods
Lentiviral vectors encoding for the LacZ gene or the fusion gene HSV-Tk/GFP were tested in vitro in human HCC cells and human
hepatocytes in primary culture and in vivo in a chemically induced rat model of HCC.
Results
We show that HIV-1-derived lentiviral vectors are efficient in transducing HCC cells
in vitro and in vivo. No significant transduction of non-tumorous hepatocytes was
observed in vivo whatever the route of administration used. Measurement of tumor growth
following direct intratumoral injection of a lentiviral vector containing the HSV-Tk
gene and GCV treatment showed a strong antitumoral efficacy in the absence of normal
liver toxicity.
Conclusions
These observations suggest that lentiviral vectors allow an antitumoral effect with
low liver toxicity when using suicide gene therapy approach and could be efficient
tools for HCC gene therapy.
Keywords
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Article info
Publication history
Accepted:
October 8,
2003
Received in revised form:
September 20,
2003
Received:
April 23,
2003
See Editorial, pages 337–340Identification
Copyright
© 2003 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
