A small interfering RNA targeting osteopontin as gastric cancer therapeutics
A small interfering RNA targeting osteopontin as gastric cancer therapeutics
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DOI：
10.1016/j.canlet.2008.07.004
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发表时间：
2008-12-08
期刊：
影响因子：
9.7
通讯作者：
Xue, Xuchao
中科院分区：
文献类型：
--
作者：
Gong, Mouchun;Lu, Zhengmao;Xue, Xuchao
骨桥蛋白（OPN）在胃癌中的表达与胃癌的发生、发展密切相关。为了更好地了解骨桥蛋白的作用，本研究采用RNA干扰（RNAi）技术在体内外抑制人胃癌细胞中骨桥蛋白的表达。用OPN小干扰RNA（siRNA）质粒稳定转染胃癌细胞株BGC-823。OPN siRNA以瞬时转染和稳定转染的方式显著降低人胃癌细胞中OPN的表达。体外下调OPN可抑制BGC-823细胞的生长、非贴壁依赖性生长、迁移和侵袭。OPN小干扰RNA通过下调MMP-2和uPA的表达，抑制NF-κ B B DNA结合活性，下调Akt磷酸化水平，从而抑制胃癌细胞的生长、迁移和侵袭。体内动物实验表明，与WT相比，OPN siRNA组的肿瘤生长受到显著抑制。用聚乙烯亚胺/OPNsi进行的肿瘤内基因治疗也导致肿瘤生长抑制和生存期延长。因此，本研究表明OPN的下调可以抑制胃癌细胞的生长、迁移和侵袭，OPN siRNA有望为胃癌的基因治疗提供新的途径。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
It has been shown that Osteopontin (OPN) protein is overexpressed in the majority of gastric cancers and associated with its pathogenesis. To better understanding of the role of OPN, RNA interference (RNAi) was used to inhibit OPN expression in the human gastric cancer cells in vitro and in vivo. BGC-823, gastric cancer cell line, was stably transfected with OPN small interfering RNA (siRNA) plasmids. OPN siRNA significantly reduced the expression of OPN in human gastric cancer cells in transient- and stable-transfection manner. In vitro down-regulation of OPN inhibited BGC-823 cell growth, anchorage-independent growth, migration and invasion. The results further showed that OPN small interfering RNA suppressed the growth, migration and invasion of gastric cancer cell through the reduction of MMP-2 and uPA expression, inhibition of NF-kappa B DNA binding activity, and down-regulation of Akt phosphorylation. In vivo animal studies showed that tumor growth was significantly inhibited in OPN siRNA group compared with WT. Intratumor gene therapy with polyethylenimine/OPNsi also resulted in tumor growth Suppression and prolonged survival. Thus, this study demonstrated that down-regulation of OPN could suppress the growth, migration and invasion of gastric cancer cells, and OPN siRNA may offer a new potential gene therapy approach for human gastric cancer in future. (C) 2008 Elsevier Ireland Ltd. All rights reserved.