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AIM: To examine the effects of Helicobacter pylori ( Hpylort)infection on the invasiveness of gastric cancer cells, and to elucidate its mechanism.METHODS: Gastric carcinoma cells, MKN-45, were incubatedwith 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 West-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and β-galactosidase activities. Lastly, the proteinDNA 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 κB (NF-κB) inhibitor; (2) the induction of MKN-45 cells invasion by H pyloriis 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 infectiontransactivates COX-2 promoter activity and increases the binding of NF-κB to this promoter.CONCLUSION: Our data demonstrate that H pylori infectionpromotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-κB and COX-2 mediated pathway,as COX-2 or NF-κB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.