Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19787

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    6P - Metformin sensitizes lung cancer cells to treatment by the tyrosine kinase inhibitor erlotinib (ID 315)

    12:30 - 13:00  |  Author(s): X. Wang
    • 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.