Predictive Role of Nuclear Factor-κB Activity in Gastric Cancer
- 1 November 2007
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Clinical Gastroenterology
- Vol. 41 (10), 894-900
- https://doi.org/10.1097/mcg.0b013e31804c707c
Abstract
Background The biologic significance of nuclear factor-κB (NF-κB) activation in human gastric cancer is unclear. We clarify the clinical significance of NF-κB activation and its relationship to Helicobacter pylori infection, a well-known pathogenesis of gastric cancer. Moreover, we examine the effects and underlying mechanisms induced by caffeic acid phenethyl ester (CAPE), an inhibitor of NF-κB, for gastric carcinoma. Methods NF-κB was located immunohistochemically in 90 human gastric cancer specimens and 50 nonmalignant gastric specimens. The correlations between NF-κB activation, pathologic staging, and H. pylori infection were analyzed. We also performed electrophoretic mobility gel shift assay, real-time reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay to evaluate the responses of AGS (a gastric adenocarcinoma epithelial cell line) human gastric cancer cells subsequent to H. pylori infection or CAPE treatment. Results Nuclear expression of NF-κB was significantly more frequently observed in gastric cancer tissues than in nonmalignant gastric tissues (31% vs. 4%, P=0.0001). The activity of NF-κB and the expressions of MMP-9, IL-1β, and IL-8 in AGS cells were activated by H. pylori infection. However, the augmented responses could be significantly reversed by CAPE treatment. Moreover, in vitro studies showed that CAPE inhibits tumor growth and capacity for invasion. Conclusions NF-κB activation is related to carcinogenesis, tumor aggression, and H. pylori infection with the increased expression of MMP-9, IL-1β, and IL-8. Moreover, NF-κB inhibitors or anti-inflammatory agents such as CAPE might be new adjuvant agent against invasive gastric carcinoma.Keywords
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