6P - Metformin sensitizes lung cancer cells to treatment by the tyrosine kinase inhibitor erlotinib

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Pathology/Molecular Biology
Presenter Xiaofei Wang
Citation Annals of Oncology (2017) 28 (suppl_2): ii1-ii5. 10.1093/annonc/mdx090
Authors X. Wang1, Y. Xiang2, B. Gao2
  • 1Department Of Respiratory Diseases, Shanghai Ruijin Hospital, Shanghai Jiao Tong University, College of Medicine, 200025 - Shanghai/CN
  • 2Shanghai Ruijin Hospital, Shanghai Jiao Tong University, College of Medicine, Shanghai/CN

Abstract

Background

Lung cancer is one of the deadliest malignant tumors with limited treatment options. Although targeted therapy, using tyrosine-kinase inhibitors, such as erlotinib, 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. Metformin (Met) has been used to treat type 2 diabetes (T2D) for nearly 60 years. Met reduces circulating glucose and insulin levels by inhibiting gluconeogenesis in the liver. Recently Met class drugs have been shown their anticancer properties, including in combination therapy, in which Met inhibits the growth of tumor initiating cells in breast cancer cell lines and prevents the relapse of tumors in vivo when combining with chemotherapy.

Methods

The effects of Met to sensitizing wild type EGFR lung cancer cells to erlotinib were examined in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), flow cytometry analysis, Western blot analysis, chemotaxis assay, as well as in vivo experiments.

Results

We found that MET sensitized lung cancer cells bearing wild-type EGFR to erlotinib treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation. As a consequence, combination of MET and erlotinib more efficiently inhibited the growth of lung cancer cells both in vitro and in mice with xenografted tumors.

Conclusions

These results suggest a novel approach to treating lung cancer cases which are originally resistant to erlotinib.

Clinical trial identification

Legal entity responsible for the study

Shanghai Ruijin Hospital

Funding

This project was supported in part by Shanghai Municipal Health and Family Planning Commission Research Grants (Youth) 20154Y0089.

Disclosure

All authors have declared no conflicts of interest.