title: FBW7 upregulation enhances cisplatin cytotoxicity in non- small cell lung cancer cells.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  FBW7 is a potential drug target for combating drug resistance and regulating the EMT in NSCLC cells.
authors.affiliation: Department of Radiation Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China E-mail : Dr_liweidong@163.com, viogro@zju.edu.cn.
authors.forename: Hao-Gang
authors.initials: HG
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Xia
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Han
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Wu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D044783:F-Box Proteins / Q000096:biosynthesis / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases; D002945:Cisplatin