Inhibition of adenovirus-mediated gene transfer of antisense matrix metalloproteinase-2 on hepatocellular carcinoma growth in vivo.
- Author:
Ming-man ZHANG
1
;
Lü-nan YAN
;
De-hua LI
;
Xing-hua GOU
;
Jiang-wen LIU
;
Zhi SU
;
Lei HAN
;
Lan-ying ZHAO
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Animals; Carcinoma, Hepatocellular; pathology; Gene Transfer Techniques; Genetic Vectors; genetics; Humans; Liver Neoplasms, Experimental; pathology; Male; Matrix Metalloproteinase 2; genetics; Mice; Mice, Inbred BALB C; Mice, Nude; Oligonucleotides, Antisense; genetics; Recombinant Proteins; genetics; Tumor Cells, Cultured
- From: Chinese Journal of Hepatology 2005;13(9):671-674
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate if a recombinant adenoviral vector carrying antisense matrix metalloproteinase-2 (MMP2) gene would inhibit the growth of hepatocellular carcinoma (HCC) in vivo.
METHODSUsing the recombinant adenoviral vector carrying antisense MMP2 gene (Ad-MMP2AS) which was constructed by us previously, to infect the human HCC cell line (Bel-7402). Then the invasiveness of the Bel-7402 cells was assayed in Matrigel, and the production of MMP2 in the Bel-7402 cells was detected with Western blotting analysis and Gelatin zymography. Then the Ad-MMP2AS-infected cells were subcutaneously inoculated in nude mice. After tumors developed, Ad-MMP2AS was injected intratumorally into pre-existing tumors. The tumors were removed, sectioned, and stained with H E.
RESULTSCompared with PBS or Ad-CMV-infected cells, the infected Bel-7402 cells with Ad-MMP2AS injections significantly reduced their MMP2 enzyme activity and invasiveness about 52.05% in Matrigel assays, and the tumor volumes in nude mice resulted in a 3.3-fold reduction. In addition, direct intratumoral injection of Ad-MMP2AS into pre-existing tumors significantly prevented further expansion of the tumor masses and resulted in a 63.06% reduction in tumor cell growth.
CONCLUSIONThe recombinant adenovirus with antisense MMP2 can effectively inhibit the invasiveness and growth of Bel-7402 cells in vitro and in vivo, and it has a therapeutic potential for HCC.
