title: Metformin inhibits the proliferation of A549/CDDP cells by activating p38 mitogen-activated protein kinase.
abstract: Metformin (Met) has been widely used in hypoglycemic therapy, and it is also able to reduce the incidence of tumors and tumor-related mortality. The present study investigated whether Met could inhibit the proliferation of lung cancer cells and enhance the sensitivity of a cisplatin-resistant lung cancer A549/CDDP cell line to cisplatin. It was found that Met treatment inhibited the proliferation of different lung cancer cells. Met inhibited the cell cycle of the A549/CDDP cells and induced apoptosis. Upon Met treatment, the A549/CDDP cells were arrested at the G1phase. The apoptosis of the A549/CDDP cells was confirmed by the appearance of apoptotic bodies in cells stained with Hoechst 33258, and by the cleavage of BH3 interacting-domain death agonist and poly (ADP-ribose) polymerase. Furthermore, results showed that the phosphorylation level of p38 mitogen-activated protein kinase (MAPK) was increased after Met treatment. The p38 MAPK inhibitor, SB203580, significantly blocked Met-induced apoptosis in the A549/CDDP cells. It was further demonstrated that Met could enhance the sensitivity of the A549/CDDP cells to cisplatin. In summary, the present study identified Met as a drug sensitizer that could improve the treatment effect of cisplatin in cisplatin-resistant lung cancers.
authors.affiliation: Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Lin
authors.affiliation: Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
keywords: cisplatin-resistant lung cancer cells; metformin; p38 MAPK