Metformin inhibits the proliferation of A549/CDDP cells by activating p38 mitogen-activated protein kinase

Wang,Yajun; Lin,Biyun; Wu,Jun; Zhang,Haitao; Wu,Bin

doi:10.3892/ol.2014.2270

Metformin inhibits the proliferation of A549/CDDP cells by activating p38 mitogen-activated protein kinase

Authors:
- Yajun Wang
- Biyun Lin
- Jun Wu
- Haitao Zhang
- Bin Wu
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Affiliations: Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China, Department of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China
Published online on: June 19, 2014 https://doi.org/10.3892/ol.2014.2270
Pages: 1269-1274

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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 G1 phase. 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.

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