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...data suggest that cyclin D1 contributes to CIN and tumorigenesis
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Mol Cancer Ther. 2012 Jan 18. [Epub ahead of print]
The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo.
Kato K,
Gong J,
Iwama H,
Kitanaka A,
Tani J,
Miyoshi H,
Nomura K,
Mimura S,
Kobayashi M,
Aritomo Y,
Kobara H,
Mori H,
Himoto T,
Okano K,
Suzuki Y,
Murao K,
Masaki T.
Source
1Gastroenterology and Neurology, Kagawa University Schhol of Medicine.
Abstract
Recent studies suggest that metformin, which is commonly used as an oral anti-hyperglycemic agent of the biguanide family, may reduce cancer risk and improve prognosis, but the mechanisms by which metformin affects various cancers, including gastric cancer, remains unknown. The goal of the present study was to evaluate the effects of metformin on human gastric cancer cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with metformin's anti-tumor effect. We used MKN1, MKN45 and MKN74 human gastric cancer cell lines to study the effects of metformin on human gastric cancer cells. Athymic nude mice bearing xenograft tumors were treated with or without metformin. Tumor growth was recorded after 4 weeks, and the expression of cell cycle-related proteins was determined. In addition, we used miRNA array tips to explore the differences among miRNAs in MKN74 cells bearing xenograft tumors treated with or without metformin in vitro and in vivo. Metformin inhibited the proliferation of MKN1, MKN45 and MKN74 in vitro.
Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially in cyclin D1, cyclin-dependent kinase4 (Cdk4), Cdk6 and by a decrease in retinoblastoma protein (Rb) phosphorylation. In addition, metformin reduced the phosphorylation of EGFR and IGF-1R in vitro and in vivo. The miRNA expression was markedly altered with the treatment of metformin in vitro and in vivo. Various miRNAs altered by metformin also may contribute to tumor growth in vitro and in vivo.
PMID:22222629 [PubMed - as supplied by publisher]