Resveratrol induces the growth inhibition of CDX-deficient gastric cancer cells using CDX2 and RUNX3 via the β-catenin/TCF4 signaling pathway

This study aimed to determine the expression levels of runt-related transcription factor 3 (RUNX3) and caudal-related homeobox 2 (CDX2) in patients with chronic gastritis, intestinal metaplasia, atypical hyperplasia, and gastric cancer (GC). To analyze the overexpression of CDX2 and the effects of resveratrol (Res) on MKN7 and TMK1 cells, immunohistochemical staining was performed to determine the protein expression levels in tissue samples. The biological activity of MKN7 and TMK1 cells was determined. Relative mRNA and protein expression levels were also determined. RUNX3 expression was positively correlated with CDX2 expression and negatively correlated with β-catenin and transcription factor 4 (TCF-4) levels in GC tissues. Interestingly, RUNX3 expression was negatively correlated with CDX2 expression in other tissues. CDX2 overexpression or Res treatment inhibited cell proliferation, migration, and invasion, while inducing cell apoptosis. Furthermore, RUNX3 and B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) expression levels were increased, while those of of β-catenin, TCF-4, and Bcl-2 were decreased in the CDX2 group. Upon treatment with lithium chloride (LiCl), the proliferation, migration, and invasion of CDX2-overexpressing MKN7 and TMK1 cells were enhanced. Our results indicate that Res inhibits the growth of MKN7 and TMK1 cells by increasing RUNX3 and CDX2 expression levels, with the potential involvement of the β-catenin/TCF-4 signaling pathway.