Abstract
Metformin is one of the most widely used anti-diabetic drugs in type-II diabetes treatment. The mechanism of decreasing blood glucose is believed to suppress hepatic gluconeogenesis by increasing muscular glucose uptake and insulin sensitivity. Recent studies suggest that metformin may reduce cancer risk; however, its anticancer mechanism in gastric cancers remains unclear. Here, we aim to evaluate the anticancer effects of metformin on human gastric adenocarcinoma (AGS) cells. Our results showed that metformin inhibited AGS cell proliferation in a dose-dependent manner. Using small-scale quantitative proteomics, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins such as 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), stress-induced phosphoprotein 1 (STIP1), and adenylyl cyclase-associated protein 1 (CAP1) were significantly altered. We found that metformin induced cell cycle arrest at the G0/G1 phase, suppressed cell migration, and affected cytoskeleton distribution. Additionally, patients with highly expressed PSMD2, STIP1, and CAP1 have a poor clinical outcome. Our study provides a novel view of developing therapies for gastric cancer.