Antitumor effect of metformin in esophageal cancer: In vitro study

Kobayashi,Mitsuyoshi; Kato,Kiyohito; Iwama,Hisakazu; Fujihara,Shintaro; Nishiyama,Noriko; Mimura,Shima; Toyota,Yuka; Nomura,Takako; Nomura,Kei; Tani,Joji; Miyoshi,Hisaaki; Kobara,Hideki; Mori,Hirohito; Murao,Koji; Masaki,Tsutomu

doi:10.3892/ijo.2012.1722

Antitumor effect of metformin in esophageal cancer: In vitro study

Authors:
- Mitsuyoshi Kobayashi
- Kiyohito Kato
- Hisakazu Iwama
- Shintaro Fujihara
- Noriko Nishiyama
- Shima Mimura
- Yuka Toyota
- Takako Nomura
- Kei Nomura
- Joji Tani
- Hisaaki Miyoshi
- Hideki Kobara
- Hirohito Mori
- Koji Murao
- Tsutomu Masaki
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Affiliations: Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan, Life Science Research Center, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan, Department of Laboratory Medicine, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
Published online on: November 29, 2012 https://doi.org/10.3892/ijo.2012.1722
Pages: 517-524

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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.

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