Oncotarget

Research Papers:

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

Xiaofei Wang, Keqiang Chen, Ying Yu, Yi Xiang, Jae Hong Kim, Wanghua Gong, Jiaqiang Huang, Guochao Shi, Qingyun Li, Min Zhou, Thomas Sayers, Poonam Tewary, Beili Gao and Ji Ming Wang _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:109068-109078. https://doi.org/10.18632/oncotarget.22596

Metrics: PDF 1614 views  |   HTML 2529 views  |   ?  


Abstract

Xiaofei Wang1,2,*, Keqiang Chen2,*, Ying Yu2,3, Yi Xiang1, Jae Hong Kim2, Wanghua Gong4, Jiaqiang Huang5, Guochao Shi1, Qingyun Li1, Min Zhou 1, Thomas Sayers4, Poonam Tewary4, Beili Gao1 and Ji Ming Wang2

1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

2Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA

3Eye Institute, Affiliated Hospital of Nantong University, Nantong 226001, China

4Basic Research Program, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA

5College of Life Sciences and Bioengineering, School of Sciences, Beijing Jiaoton University, Beijing 100044, China

*These authors have contributed equally to this work

Correspondence to:

Ji Ming Wang, email: [email protected]

Beili Gao, email: [email protected]

Keywords: lung cancer; metformin; EGFR; erlotinib; phosphorylation

Received: July 14, 2017     Accepted: August 21, 2017     Published: November 21, 2017

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 22596