| Summary: | 碩士 === 國立臺灣大學 === 分子與細胞生物學研究所 === 101 === Metformin is one of the most widely used anti-diabetic drugs in type II diabetes treatment. The mechanism of lowering blood glucose is believed to be involved in suppressing hepatic gluconeogenesis, increasing muscular glucose uptake and enhancing insulin sensitivity. Recent studies suggest that metformin may reduce cancer risk, but the mechanism of anticancer action remains unclear, especially in gastric cancer. In our studies, we aim to evaluate the anticancer effects of metformin on human gastric cancer AGS cells, and use isobaric Tagging for Relative and Absolute Quantitation (iTRAQ)-based quantitative proteomics to further study the anticancer mechanism. Our results showed that metformin inhibited AGS cell proliferation in a dose dependent manner, induced AGS cell cycle arrest at G0/G1 phase, suppressed cell migration ability, and affected the distribution of cytoskeleton. Using quantitative proteomics approach, we identified 177 differentially expressed proteins upon metformin treatment; among these, nine proteins are significantly altered in expression level, including four up-regulated proteins (Prohibitin-2, Heterogeneous nuclear ribonucleoprotein A/B (hnRNP A/B), Clathrin heavy chain 1, Macrophage migration inhibitory factor (MIF)) and five down-regulated proteins (T-complex protein 1 subunit epsilon, 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), Stress-induced-phosphoprotein 1 (STIP1), Polypyrimidine tract-binding protein 1, Adenylyl cyclase-associated protein 1 (CAP1)). In previous study, STIP1, CAP1 and PSMD2 were reported associated with cancer cell proliferation and motility. The expression level of STIP1, CAP1 and PSMD2 were further validated by immunoblotting and consistent with the proteomic results. Our findings imply that metformin might inhibit cell proliferation and migration in AGS cells by suppressing STIP1, CAP1 and PSMD2. Although more animal and clinical studies are needed to confirm the effects of metformin, our studies may provide a new way for developing therapies for gastric cancer.
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