ABSTRACT
Background: Studies have showed that proton pump inhibitor (PPI) can inhibit the expression of V-ATPases and influence the glycolysis of gastric cancer cells. V-ATPases have important significance on malignant biological behavior of tumor. Aims: To explore the mechanisms of PPI on gastric cancer via inhibiting glycolysis and glutamine metabolism. Methods: In the cell experiment, gastric cancer cell lines were cultured with PPI and knockdown of related molecules, cell proliferation was determined by CCK-8 assay, cell apoptosis was detected by flow cytometry. mRNA and protein expressions of related molecules were detected by quantitative PCR and Western blotting, respectively. In the animal experiment, nude mice were divided into blank control group, 0.9% NaCl solution group, pantoprazole sodium group, and PKM2 group, body weight, feeding behavior, tumor size and expressions of related pathway molecule in tumor tissue were compared. Results: PPI could inhibit the proliferation and induce apoptosis of gastric cancer cells. PPI could suppress the expression of related molecules of glycolysis and glutamine metabolism. Knocking down PKM2 or PI3K could inhibit proliferation and induce apoptosis of gastric cancer cells. Silencing V-ATPases inhibited the expression of related molecules of glycolysis and glutamine metabolism in gastric cancer cells. PPI therapy delayed tumor growth and reduced cachexia in tumor-bearing mice. Conclusions: PPI may inhibit cell proliferation and induce cell apoptosis by influencing glycolysis and glutamine metabolism of gastric cancer cells via suppressing V-ATPases and PI3K pathway, thus to play an anti-tumor role.