Suppression of matrix metalloproteinase-9 expression by RNA interference inhibits SGC7901 gastric adenocarcinoma cell growth and invasion in vitro and in vivo

被引:0
作者
Fengjuan Zhao
Qingyu Zhang
Chunsheng Kang
Xiaowei Cui
Tao Wang
Peng Xu
Xuan Zhou
Jian Liu
Xiaomei Song
机构
[1] Tianjin Medical University General Hospital,Department of Gastroenterology
[2] Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology,Department of Neurosurgery
[3] Tianjin Neurological Institute,undefined
来源
Medical Oncology | 2010年 / 27卷
关键词
RNA interference; Gastric cancer; Matrix metalloproteinase-9; Invasion; Growth; Gene therapy;
D O I
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中图分类号
学科分类号
摘要
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.
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页码:774 / 784
页数:10
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共 71 条
  • [1] Tajima Y(2006)Gastric and intestinal phenotypic marker expression in early differentiated-type tumors of the stomach: clinicopathologic significance and genetic background Clin Cancer Res 12 6469-6479
  • [2] Ma JL(2006)Analysis of mortality trend of cancer from 1980 to 2002 in Linqu County Shandong Province Zhonghua Yufang Yixue Zazhi 40 405-408
  • [3] Giese A(2003)Cost of migration: invasion of malignant gliomas and implications for treatment J Clin Oncol 21 1624-1636
  • [4] Bjerkvig R(2008)Correlation of integrin beta3 mRNA and vascular endothelial growth factor protein expression profiles with the clinicopathological features and prognosis of gastric carcinoma World J Gastroenterol 14 421-427
  • [5] Berens ME(2005)DNA ploidy analysis and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma World J Gastroenterol 11 5592-5600
  • [6] Westphal M(2007)RNAi-mediated abrogation of cathepsin B and MMP-9 gene expression in a malignant meningioma cell line leads to decreased tumor growth, invasion and angiogenesis Int J Oncol 31 1039-1050
  • [7] Li SG(2007)RNAi-mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease-9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth Int J Cancer 121 2307-2316
  • [8] Zhang JF(1998)Potent and specific genetic interference by double-stranded RNA in Nature 391 806-811
  • [9] Tummalapalli P(2000)The delivery of antisense therapeutics Adv Drug Deliv Rev 44 3-21
  • [10] Kunigal S(2001)The cellular delivery of antisense oligonucleotides and ribozymes Drug Discov Today 6 303-315