Suppression of matrix metalloproteinase-9 expression by RNA interference inhibits SGC7901 gastric adenocarcinoma cell growth and invasion in vitro and in vivo.
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.
Zhao
Fengjuan
F
Department of Gastroenterology, Tianjin Medical University General Hospital, 154 An-Shan Road, Heping District, Tianjin, 300052, People's Republic of China.
Zhang
Qingyu
Q
Kang
Chunsheng
C
Cui
Xiaowei
X
Wang
Tao
T
Xu
Peng
P
Zhou
Xuan
X
Liu
Jian
J
Song
Xiaomei
X
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology; D002465:Cell Movement; D015536:Down-Regulation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; D020320:Oligoribonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9
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