Suppression of matrix metalloproteinase-9 expression by RNA interference inhibits SGC7901 gastric adenocarcinoma cell growth and invasion in vitro and in vivo
Suppression of matrix metalloproteinase-9 expression by RNA interference inhibits SGC7901 gastric adenocarcinoma cell growth and invasion in vitro and in vivo
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DOI：
10.1007/s12032-009-9285-x
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发表时间：
2010-09-01
期刊：
影响因子：
3.4
通讯作者：
Song, Xiaomei
中科院分区：
文献类型：
--
作者：
Zhao, Fengjuan;Zhang, Qingyu;Song, Xiaomei
基质金属蛋白酶-9 (MMP-9) 被认为是通过分解 IV 型胶原蛋白来降解细胞外基质 (ECM) 的关键酶。上调的 MMP-9 促进胃腺癌的生长和侵袭。本研究旨在阻断胃腺癌细胞中MMP-9的表达，以抑制肿瘤的生长和侵袭。通过在组织阵列上应用免疫组织化学，再次证实了 MMP-9 表达与肿瘤病理学之间的关联。靶向人 MMP-9 的小干扰 RNA (siRNA) 用于抑制 SGC7901 人胃腺癌细胞中的基因表达。在特定的 siRNA 靶向细胞中，细胞生长和侵袭受到显着抑制。此外，我们还建立了 SGC7901 皮下小鼠模型来观察 RNA 干扰 (RNAi) 的抗肿瘤作用。数据显示，MMP-9 siRNA 治疗小鼠的肿瘤质量明显小于对照小鼠的肿瘤质量。 MMP-9 siRNA处理的细胞中血管内皮生长因子和增殖细胞核抗原的表达下调。我们的结果表明，MMP-9靶向RNAi能够在体外和体内成功抑制MMP-9基因表达并抑制SGC7901胃腺癌的细胞生长和侵袭。 MMP-9是胃腺癌的潜在治疗靶点。
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.