title: Metformin inhibits growth of lung adenocarcinoma cells by inducing apoptosis via the mitochondria-mediated pathway.
abstract: Metformin is commonly used to treat type II diabetes, although it may also reduce the risk of cancer and improve the associated prognosis. However, its mode of action in cancer remains unclear. The present study evaluated the effects of metformin on lung adenocarcinoma A549 cells and identified molecular mechanisms of metformin activity. The A549 cells were treated with metformin at different concentrations and cell viability was assayed by using an MTT assay. The cell cycle and the apoptosis rate were assayed by flow cytometry. Nude mice were transplanted with A549 cells and the tumor growth inhibition rate was detected. Once the A549 cells had been treated with 20 mM metformin for 48 h, the cell cycle was arrested in the G0/Glphase and the apoptosis rate was 20.57±3.16%. The expression of the B-cell lymphoma (Bcl)-2 and Bcl-extra large proteins was downregulated following metformin treatment, while Bax protein expression was signiﬁcantly increased. Tumor size in the high-dose metformin and cisplatin plus metformin groups was significantly smaller, and the inhibition rates were 41.3 and 72.9%, respectively, compared with the control group. These results indicated that metformin displays anticancer activity against lung adenocarcinoma by causing G1arrest of the cell cycle and subsequent cell apoptosis through the mitochondria-dependent pathway in A549 cells. Furthermore, it was found that metformin dramatically inhibited lung adenocarcinoma tumor growthin vivo. These data suggest that metformin may become a potential cytotoxic drug in the prevention and treatment of lung adenocarcinoma.
authors.affiliation: Department of Medical Oncology, Binzhou Tuberculosis Control Center, Binzhou Medical College, Binzhou, Shandong 250000, P.R. China.
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiology, Binzhou People's Hospital, Binzhou, Shandong 250000, P.R. China.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Binzhou Tuberculosis Control Center, Binzhou Medical College, Binzhou, Shandong 250000, P.R. China.
authors.forename: Decui
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Binzhou Tuberculosis Control Center, Binzhou Medical College, Binzhou, Shandong 250000, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oncology, RuiJin Hospital, Shanghai JiaoTong University, Shanghai 200001, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Hu
keywords: apoptosis; lung adenocarcinoma; metformin; mitochondrion-mediated pathway