Helicobacter pylori promote gastric cancer cells invasion through a NF-κB and COX-2-mediated pathway
Helicobacter pylori promote gastric cancer cells invasion through a NF-κB and COX-2-mediated pathway
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DOI：
10.3748/wjg.v11.i21.3197
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发表时间：
2005-06-07
影响因子：
4.3
通讯作者：
Chen, Gran-Hum
中科院分区：
文献类型：
--
作者：
Wu, Chun-Ying;Wang, Chau-Jong;Chen, Gran-Hum
目的：探讨幽门螺杆菌(Hp)感染对胃癌细胞侵袭能力的影响，并探讨其作用机制。方法：将CagA阳性的Hp与人胃癌MKN-45细胞共同孵育，Matrigel分析检测细胞侵袭力。免疫印迹法检测基质金属蛋白酶-9、血管内皮生长因子和环氧合酶-2的表达，荧光素酶和β-半乳糖苷酶活性检测环氧合酶-2启动子的转录活性。结果：(1)CagA阳性的幽门螺杆菌与MKN-45细胞共孵育可显著促进MKN-45细胞的侵袭，这种作用可被COX-2抑制剂NS-398或核因子-kappaB抑制剂PDTC所减弱；(2)H Pylori诱导MKN-45细胞侵袭与COX-2、MMP-9和VEGF蛋白表达的增加有关，而NS-398或PDTC的共同孵育可显著减弱这种作用；(3)幽门螺杆菌感染反式激活COX-2启动子活性，增加核因子-kappaB与该启动子的结合。结论：幽门螺杆菌感染通过激活基质金属蛋白酶-9和血管内皮生长因子的表达促进胃上皮细胞的侵袭。这些作用可能是通过NF-kappa B和COX-2介导的途径实现的，因为COX-2或NF-kappa B抑制剂显著降低了胃癌细胞的侵袭力，并抑制了基质金属蛋白酶-9和血管内皮生长因子的表达。(C)2005年WJG Press和Elsevier Inc.保留所有权利。
AIM: To examine the effects of Helicobacter pylori (H pylori) infection on the invasiveness of gastric cancer cells, and to elucidate its mechanism.METHODS: Gastric carcinoma cells, MKN-45, were incubated with CagA-positive H pylori, and cell invasion was determined by Matrigel analysis. The expression of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and beta-galactosidase activities. Lastly, the protein-DNA interaction was confirmed by an electrophoretic mobility shift assay.RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC, a nuclear factor kappa B (NF-kappa B) inhibitor; (2) the induction of MKN-45 cells invasion by H pylori is associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects; (3) H pylori infection transactivates COX-2 promoter activity and increases the binding of NF-kappa B to this promoter.CONCLUSION: Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-kappa B and COX-2 mediated pathway, as COX-2 or NF-kappa B inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.