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FBW7 Upregulation Enhances Cisplatin Cytotoxicity in Non-small Cell Lung Cancer Cells

  • Yu, Hao-Gang (Department of Radiation Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Wei, Wei (Department of Radiation Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Xia, Li-Hong (Department of Radiation Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Han, Wei-Li (Department of Cardiothoracic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Zhao, Peng (Department of Radiation Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Wu, Sheng-Jun (Department of Cardiothoracic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Li, Wei-Dong (Department of Cardiothoracic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University) ;
  • Chen, Wei (Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University)
  • Published : 2013.11.30

Abstract

Introduction: Lung cancer is extremely harmful to human health and has one of the highest worldwide incidences of all malignant tumors. Approximately 80% of lung cancers are classified as non-small cell lung cancers (NSCLCs). Cisplatin-based multidrug chemotherapy regimen is standard for such lesions, but drug resistance is an increasing problem. F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein family that regulates cell cycle progression, and cell growth and differentiation. FBW7 also functions as a tumor suppressor. Methods: We used cell viability assays, Western blotting, and immunofluorescence combined with siRNA interference or plasmid transfection to investigate the underlying mechanism of cisplatin resistance in NSCLC cells. Results: We found that FBW7 upregulation significantly increased cisplatin chemosensitivity and that cells expressing low levels of FBW7, such as NCI-H1299 cells, have a mesenchymal phenotype. Furthermore, siRNA-mediated silencing or plasmid-mediated upregulation of FBW7 resulted in altered epithelial-mesenchymal transition (EMT) patterns in NSCLC cells. These data support a role for FBW7 in regulating the EMT in NSCLC cells. Conclusion: FBW7 is a potential drug target for combating drug resistance and regulating the EMT in NSCLC cells.

Keywords

FBW7;NSCLC cells;cisplatin;epithelial-mesenchymal transition;drug resistance

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