FBW7 Upregulation Enhances Cisplatin Cytotoxicity in Nonsmall Cell Lung Cancer Cells


Introduction: Lung cancer is extremely harmful to human health and has one of the highest worldwideincidences of all malignant tumors. Approximately 80% of lung cancers are classified as non-small cell lungcancers (NSCLCs). Cisplatin-based multidrug chemotherapy regimen is standard for such lesions, but drugresistance is an increasing problem. F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-boxprotein family that regulates cell cycle progression, and cell growth and differentiation. FBW7 also functions as atumor suppressor.
Methods: We used cell viability assays, Western blotting, and immunofluorescence combinedwith siRNA interference or plasmid transfection to investigate the underlying mechanism of cisplatin resistancein NSCLC cells.
Results: We found that FBW7 upregulation significantly increased cisplatin chemosensitivity andthat 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-mesenchymaltransition (EMT) patterns in NSCLC cells. These data support a role for FBW7 in regulating the EMT in NSCLCcells.
Conclusion: FBW7 is a potential drug target for combating drug resistance and regulating the EMT inNSCLC cells.