Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor.

Abstract:

:Specificity is a prerequisite for systemic gene therapy of hepatocarcinoma. In vitro, the tumor-specific viral death effector Apoptin selectively induces apoptosis in malignant hepatic cells. Intratumoral treatment of xenografted subcutaneous hepatomas with Apoptin results in tumor regression. Here, we report a systemic delivery vehicle containing the Apoptin gene linked to asialoglycoprotein (Asor), which targets asialoglycoprotein receptor (ASGPR) present only on the surface of hepatocytes. In vitro, the protein-DNA complex Asor-Apoptin induced apoptosis in HepG2 hepatocarcinoma cells but not in normal L-02 hepatocytes. Non-hepatocyte-derived tumorigenic human A549 cells lacking the membrane ASGPR were not affected by Asor-Apoptin. In vivo systemic delivery of Asor-Apoptin via the tail vein into mice bearing in situ hepatocarcinoma resulted in specific and efficient distribution of Apoptin in both hepatocarcinoma cells and normal hepatocytes. Five days after injection of Asor-Apoptin, the in situ hepatocarcinomas showed significant signs of regression, whereas the surrounding normal hepatocytes did not. Systemically delivered Asor-LacZ expressing non-apoptotic LacZ gene did not inhibit tumor growth. Our data reveal that systemic delivery of Asor-Apoptin specifically induces apoptosis in malignant hepatocytes and thus constitutes a powerful and safe therapeutics against hepatocarcinomas.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Peng DJ,Sun J,Wang YZ,Tian J,Zhang YH,Noteborn MH,Qu S

doi

10.1038/sj.cgt.7700985

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

66-73

issue

1

eissn

0929-1903

issn

1476-5500

pii

7700985

journal_volume

14

pub_type

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