Predictive role of nuclear factor-kappaB activity in gastric cancer: a promising adjuvant approach with caffeic acid phenethyl ester.

BACKGROUND

The biologic significance of nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear. We clarify the clinical significance of NF-kappaB 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-kappaB, for gastric carcinoma.

METHODS

NF-kappaB was located immunohistochemically in 90 human gastric cancer specimens and 50 nonmalignant gastric specimens. The correlations between NF-kappaB 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-kappaB was significantly more frequently observed in gastric cancer tissues than in nonmalignant gastric tissues (31% vs. 4%, P=0.0001). The activity of NF-kappaB and the expressions of MMP-9, IL-1beta, 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-kappaB activation is related to carcinogenesis, tumor aggression, and H. pylori infection with the increased expression of MMP-9, IL-1beta, and IL-8. Moreover, NF-kappaB inhibitors or anti-inflammatory agents such as CAPE might be new adjuvant agent against invasive gastric carcinoma.