Author of

• 13580

  +

  P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 13692

    +

    P1.04-112 - Rapamycin Attenuated Epithelial-Mesenchymal Transition in Lung Cancer Cells (ID 144)

    09:30 - 09:30  |  Author(s): L. Lin
    • Abstract

    Background:
    Mammalian target of rapamycin (mTOR) plays an important role in the physiological regulation of cell growth and development. Dysregulation of mTOR signaling frequently occurs in malignancies, including lung cancer. Inhibition of mTOR is a promising therapeutic strategy against lung cancer shown by clinical trials. But its mechanism remains unclear. Epithelial–mesenchymal transition (EMT) is critical in the pathogenesis of lung carcinoma. This study aimed to examine the effect of rapamycin on TGF-β1-induced EMT in lung carcinoma cells.
    
    Methods:
    Lung carcinoma cells (A549 cells) were pre-incubated with rapamycin and stimulated with TGF-β1. Morphological changes were observed under microscope. Cell phenotype markers were analyzed by western blotting and immunocytochemistry. F-actin cytoskeleton rearrangement was examined by phalloidin staining. Cell migration ability was measured by cell scratch test. The phosphorylated Smad2/3 and mTOR were measured by western blotting.
    
    Results:
    Firstly, TGF-β1 induced EMT in lung carcinoma cells confirmed by the morphological changes, as well as the down-regulation of epithelial marker (E-cadherin) and the up-regulation of mesenchymal marker (fibronectin) and the F-actin cytoskeleton rearrangement during which the mTOR pathway was activated. Secondly, rapamycin decreased the degree of TGF-β1 induced morphological changes, attenuated the down-regulation of E-cadherin and up-regulation of fibronectin, and inhibited the F-actin cytoskeleton rearrangement. Moreover, rapamycin inhibited the migration ability of lung carcinoma cells. Further research on mechanism showed that the attenuation TGF-β1-induced-EMT by rapamycin was associated with the down-regulation of the phosphorylation of Smad2/3.
    
    Conclusion:
    Rapamycin attenuated TGF-β1- induced EMT and migration in lung carcinoma cells which was mediated, at least in part, by decrease of Smad2/3 phosphorylation.