[Recombinant adenovirus vectors carrying antisense matrix metalloproteinase-2 inhibits hepatocellular carcinoma growth in vivo].
OBJECTIVE
To investigate the inhibitory effect of a recombinant adenoviral vector carrying antisense matrix metalloproteinase-2(MMP2) on the growth of hepatocellular carcinoma(HCC) in vivo.


METHODS
The recombinant adenoviral vector carrying antisense MMP2(Ad-MMP2(AS))which had been constructed by us in readiness was used 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 blot analysis and Gelatin zymography. After the Ad-MMP2(AS)-infected Bel-7402 cells being subcutaneously inoculated in nude mice, the production of tumors was under observation, and then Ad-MMP2(AS) was injected intratumorally into the pre-existing tumors.


RESULTS
Compared with PBS or Ad-CMV-infected cells, infection of Bel-7402 cells with Ad-MMP2(AS) significantly reduced MMP2 enzyme activity, the invasiveness resulted in 52% reduction in Matrigel assays, and the tumor volume displayed a 4.3-fold reduction in nude mice. In addition, direct intratumoral injection of Ad-MMP2(AS) into pre-existing tumors significantly impaired the further expansion of the tumor mass and resulted in a 63% 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 has a therapeutic potential for HCC.
Zhang
Ming-man
MM
Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Yan
Lü-nan
LN
Li
De-hua
DH
Liu
Jiang-wen
JW
Gou
Xing-hua
XH
Han
Lei
L
Su
Zhi
Z
Zhao
Lan-ying
LY
Hu
Hai-yang
HY
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016372:RNA, Antisense / Q000235:genetics* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use
D016372:RNA, Antisense; D011994:Recombinant Proteins; D020778:Matrix Metalloproteinase 2