Effect of pantoprazole on human gastric adenocarcinoma SGC7901 cells through regulation of phospho‑LRP6 expression in Wnt/β-catenin signaling.

Recent studies have found that an acidic tumor microenvironment is the key to managing cancer progression and metastasis. Our previous study found that proton pump inhibitors (PPIs) inhibit the expression of vacuolar-ATPases (V-ATPases) and reverse the transmembrane pH gradient. The present study was conducted to explore the effect of pantoprazole on gastric adenocarcinoma through the regulation of Wnt/β-catenin signaling. We used SGC7901 human gastric cancer cells as an in vitro model to study the effect of pantoprazole. The antiproliferative, pro-apoptotic and anti‑invasive effects of pantoprazole were examined. The effects of pantoprazole on the expression of the Wnt/β-catenin signaling pathway were also studied by western blotting. Our study found that pantoprazole inhibited the proliferation and induced the apoptosis of SGC7901 human gastric cancer cells. The expression of V-ATPases was decreased following treatment with pantoprazole. Further study found that pantoprazole treatment caused a decrease in phospho-LRP6, but not in LRP6. β-catenin in Wnt/β-catenin signaling and its target genes c-Myc and cyclin D1 were also decreased upon the inhibition of V-ATPases. Therefore, pantoprazole could be characterized as a V-ATPase inhibitor for treating gastric cancer by inhibiting the phosphorylation of LRP6 in Wnt/β-catenin signaling.