title: Antitumor effect of metformin in esophageal cancer: in vitro study.
abstract: Recent studies suggest that metformin, which is a member of the biguanide family and commonly used as an oral anti-hyperglycemic agent, may reduce cancer risk and improve prognosis of numerous types of cancer. However, the mechanisms underlying the antitumor effect of metformin on esophageal cancer remain unknown. The goal of the present study was to evaluate the effects of metformin on the proliferation of human ESCC in vitro, and to study changes in the expression profile of microRNAs (miRNAs), since miRNAs have previously been associated with the antitumor effects of metformin in other human cancers. The human ESCC cell lines T.T, KYSE30 and KYSE70 were used to study the effects of metformin on human ESCC in vitro. In addition, we used miRNA array tips to explore the differences between miRNAs in KYSE30 cells with and without metformin treatment. Metformin inhibited the proliferation of T.T, KYSE30 and KYSE70 cells in vitro. Metformin blocked the cell cycle in G0/G1 in vitro. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, as well as decreases in cyclin-dependent kinase (Cdk)4, Cdk6 and phosphorylated retinoblastoma protein (Rb). In addition, the expression of miRNAs was markedly altered with the treatment of metformin in vitro. Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6.
authors.affiliation: Department of Gastroenterology and Neurology, Faculty of Medicine,                     Kagawa University, Kagawa 761-0793, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Kato
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Iwama
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fujihara
authors.forename: Noriko
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Shima
authors.initials: S
authors.lastname: Mimura
authors.forename: Yuka
authors.initials: Y
authors.lastname: Toyota
authors.forename: Takako
authors.initials: T
authors.lastname: Nomura
authors.forename: Kei
authors.initials: K
authors.lastname: Nomura
authors.forename: Joji
authors.initials: J
authors.lastname: Tani
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Hideki
authors.initials: H
authors.lastname: Kobara
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
mesh_terms: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D035683:MicroRNAs; D008687:Metformin