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Published on: October 27, 2014
FBW7 upregulation enhances cisplatin cytotoxicity in non- small cell lung cancer cells
Hao-Gang Yu1, Wei Wei, Li-Hong Xia
1Department 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.
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.
