title: Effect of pantoprazole on human gastric adenocarcinoma SGC7901 cells through regulation of phospho‑LRP6 expression in Wnt/β-catenin signaling.
abstract: 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.
authors.affiliation: Department of Digestive Disease, Gastrointestinal Center, Jiangyin People's Hospital, Medical School of the University of Southeast China, Jiangyin, Jiangsu 214400. PR China. shenwd2003@yahoo.com.cn
authors.forename: Weidong
authors.initials: W
authors.lastname: Shen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Shen
authors.forename: Shuling
authors.initials: S
authors.lastname: Huang
authors.forename: Huimin
authors.initials: H
authors.lastname: Guo
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000096:biosynthesis* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D000077402:Pantoprazole; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000187:drug effects; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1; D000077402:Pantoprazole; D025262:Vacuolar Proton-Translocating ATPases