title: Metformin inhibits gastric cancer via the inhibition of HIF1α/PKM2 signaling.
abstract: Recent evidence suggests that anti-diabetic drug metformin prevents cancer progression, but the mechanism by which metformin inhibits tumor growth remains elusive. In this study, we investigated the anticancer role of metformin in gastric cancer and explored the underlying mechanism. The expression of hypoxia inducible factor 1α (HIF1α) and pyruvate kinase M2 (PKM2) in different stages of gastric cancer tissues was detected by immunohistochemistry. Gastric cancer cell viability was evaluated by CCK-8 assay; apoptosis and cell cycle were analyzed by flow cytometry. The expression of PI3K, Akt, HIF1α, PARP, PKM2 and COX in gastric cancer cells was detected by immunofluorescence and Western blot analysis. We found that HIF1α and PKM2 protein expression levels were higher in advanced gastric cancer tissues than in gastritis tissues. Metformin reduced gastric cancer cell viability, invasion and migration. Metformin induced apoptosis and cell cycle arrest in part through inhibiting PARP expression. Metformin downregulated PI3K, Akt, HIF1α, PARP, PKM2 and COX expression. Moreover, overexpression of HIF1α increased gastric cancer cell viability, invasion and migration. In summary, metformin has profound antitumor effect for gastric cancer by inducing intrinsic apoptosis via the inhibition of HIF1α/PKM2 signaling pathway.
authors.affiliation: Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University Nanjing, China ; Department of Gastroenterology, First People's Hospital of Xuzhou Xuzhou, China.
authors.forename: Guangxia
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University Nanjing, China.
authors.forename: Wan
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University Nanjing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University Nanjing, China.
authors.forename: Kangqi
authors.initials: K
authors.lastname: Bian
authors.affiliation: Department of Gastroenterology, Xuzhou Central Hospital, Clinical College of Xuzhou Medical College Xuzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pathology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University Nanjing, China ; Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University Nanjing, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
keywords: Metformin; gastric cancer; hypoxia inducible factor 1α; pyruvate kinase M2