Metformin sensitizes lung cancer cells to treatment by the tyrosine kinase inhibitor erlotinib

Author:

Wang, Xiaofei

Chen, Keqiang

Yu, Ying

Xiang, Yi

Kim, Jae Hong

Gong, Wang

Huang, Jiaqiang

Shi, Guochao

Li, Qingyun

Zhou, Min

Sayers, Thomas

Tewary, Poonam

Gao, Beili

Wang, Jiming
Author Address

Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China., Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, China., Basic Research Program, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA., College of Life Sciences and Bioengineering, School of Sciences, Beijing Jiaoton University, Beijing 100044, China.,

Abstract:

Lung cancer is one of the deadliest malignant tumors with limited treatment options. Although targeted therapy, using tyrosine-kinase inhibitors such as erlotinib (Erlo), has shown therapeutic benefit, only 15 % patients with mutated epidermal growth factor receptor (EGFR) in lung cancer cells are sensitive. Therefore, additional therapeutic strategy should be developed. In this study, we found that metformin (Met), which is widely used for the treatment of type 2 diabetes (T2D), sensitized lung cancer cells bearing wild-type EGFR to Erlo treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation. As a consequence, combination of Met and Erlo more efficiently inhibited the growth of lung cancer cells both in vitro and in mice with xenografted tumors. Our results suggest a novel approach to treating lung cancer cases which are originally resistant to Erlo.

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Author Address