Antiproliferative action of metformin in human lung cancer cell lines

作者：Ashinuma Hironori; Takiguchi Yuichi^*; Kitazono Satoru; Kitazono Saitoh Miyako; Kitamura Atsushi; Chiba Tetsuhiro; Tada Yuji; Kurosu Katsushi; Sakaida Emiko; Sekine Ikuo; Tanabe Nobuhiro; Iwama Atsushi; Yokosuka Osamu; Tatsumi Koichiro

来源：Oncology Reports, 2012, 28(1): 8-14.

DOI：10.3892/or.2012.1763

• metformin
• lung cancer
• cisplatin
• apoptosis
• cell line
• cell cycle

The oral antidiabetic agent metformin has anticancer properties, probably via adenosine monophosphate-activated protein kinase activation. In the present study, growth inhibition was assessed by a clonogenic and by a cell survival assay, apoptosis induction was assessed by Hoechst staining and caspase activities and cell cycle alteration after exposure to metformin, and the interaction of metformin with cisplatin in vitro were elucidated in four human lung cancer cell lines representing squamous, adeno-, large cell and small cell carcinoma. Clonogenicity and cell proliferation were inhibited by metform in in all the cell lines examined. This inhibitory effect was not specific to cancer cells because it was also observed in a non-transformed human mesothelial cell line and in mouse fibroblast cell lines. Inhibition of clonogenicity was observed only when the cells were exposed to metformin for a long period, (10 days) and the surviving fraction, obtained after inhibiting proliferation by increasing the dose, reached a plateau at approximately 0.1-0.3, indicating the cytostatic characteristics of metformin. Metformin induced significant apoptosis only in the small cell carcinoma cell line. A tendency of cell cycle accumulation at the G0/G1 phase was observed in all four cell lines. Cisplatin, in a dose-dependent manner, severely antagonized the growth inhibitory effect of metformin, and even reversed the effect in three cell lines but not in the adenocarcinoma cell line. The present data obtained using various histological types of human lung cancer cell lines in vitro illustrate the cytostatic nature of metformin and its cytoprotective properties against cisplatin.

• 出版日期2012-7