1. [Recombinant adenovirus vectors carrying antisense matrix metalloproteinase-2 inhibits hepatocellular carcinoma growth in vivo].
- Author
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Zhang MM, Yan LN, Li DH, Liu JW, Gou XH, Han L, Su Z, Zhao LY, and Hu HY
- Subjects
- Animals, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, Genetic Therapy, Genetic Vectors, Humans, Male, Matrix Metalloproteinase 2 genetics, Mice, Mice, Nude, Neoplasm Transplantation, RNA, Antisense therapeutic use, Recombinant Proteins biosynthesis, Recombinant Proteins genetics, Recombinant Proteins therapeutic use, Adenoviridae genetics, Liver Neoplasms pathology, Matrix Metalloproteinase 2 biosynthesis, Matrix Metalloproteinase 2 therapeutic use, RNA, Antisense genetics
- Abstract
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., Conclusion: 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.
- Published
- 2006