[Inhibition of adenovirus-mediated gene transfer of antisense matrix metalloproteinase-2 on hepatocellular carcinoma growth in vivo].
OBJECTIVE
To investigate if a recombinant adenoviral vector carrying antisense matrix metalloproteinase-2 (MMP2) gene would inhibit the growth of hepatocellular carcinoma (HCC) in vivo.


METHODS
Using 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.


RESULTS
Compared 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.


CONCLUSIONS
The 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.
Zhang
Ming-man
MM
Department of General Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.
Yan
Lü-nan
LN
Li
De-hua
DH
Gou
Xing-hua
XH
Liu
Jiang-wen
JW
Su
Zhi
Z
Han
Lei
L
Zhao
Lan-ying
LY
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016376:Oligonucleotides, Antisense / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins; D020778:Matrix Metalloproteinase 2