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Suppression of matrix metalloproteinase-9 expression by RNA interference inhibits SGC7901 gastric adenocarcinoma cell growth and invasion in vitro and in vivo.
- Source :
-
Medical oncology (Northwood, London, England) [Med Oncol] 2010 Sep; Vol. 27 (3), pp. 774-84. Date of Electronic Publication: 2009 Aug 13. - Publication Year :
- 2010
-
Abstract
- Matrix metalloproteinase-9 (MMP-9) is considered the key enzyme that degrades extracellular matrix (ECM) via breaking down type IV collagens. Up-regulated MMP-9 promotes growth and invasion of gastric adenocarcinomas. The present study is to block MMP-9 expression in gastric adenocarcinoma cells in order to inhibit tumor growth and invasion. The association between MMP-9 expression and tumor pathology was reconfirmed by applying immunohistochemistry on tissue arrays. Small interference RNAs (siRNA) targeted on human MMP-9 were used to suppress gene expression in SGC7901 human gastric adenocarcinoma cells. Cell growth and invasion were significantly inhibited in specific siRNA-targeted cells. In addition, we generate a SGC7901-subcutaneous mice model to observe anti-tumor effects from RNA interference (RNAi). Data showed tumor masses in MMP-9 siRNA-treated mice were significantly smaller than those in control mice. The expression of vascular endothelial growth factor and proliferating cell nuclear antigen were down-regulated in MMP-9 siRNA treated cells. Our results demonstrate that MMP-9 targeted RNAi is able to successfully suppress MMP-9 gene expression and inhibit cell growth and invasion of SGC7901 gastric adenocarcinoma in vitro and in vivo. MMP-9 is a potential therapeutic target for gastric adenocarcinomas.
- Subjects :
- Adenocarcinoma enzymology
Adenocarcinoma genetics
Adenocarcinoma pathology
Animals
Cell Division
Cell Line, Tumor drug effects
Cell Line, Tumor enzymology
Cell Movement
Down-Regulation drug effects
Enzyme Induction drug effects
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Matrix Metalloproteinase 9 biosynthesis
Matrix Metalloproteinase 9 genetics
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Proteins biosynthesis
Neoplasm Proteins genetics
Oligoribonucleotides, Antisense pharmacology
Proliferating Cell Nuclear Antigen biosynthesis
RNA, Small Interfering pharmacology
Stomach Neoplasms enzymology
Stomach Neoplasms genetics
Stomach Neoplasms pathology
Vascular Endothelial Growth Factor A biosynthesis
Xenograft Model Antitumor Assays
Adenocarcinoma therapy
Genetic Therapy
Matrix Metalloproteinase Inhibitors
Neoplasm Proteins antagonists & inhibitors
Oligoribonucleotides, Antisense therapeutic use
RNA Interference
RNA, Small Interfering therapeutic use
Stomach Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1559-131X
- Volume :
- 27
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Medical oncology (Northwood, London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 19680827
- Full Text :
- https://doi.org/10.1007/s12032-009-9285-x