Yu Hao-Gang, Wei Wei, Xia Li-Hong, Han Wei-Li, Zhao Peng, Wu Sheng-Jun, Li Wei-Dong, Chen Wei
Department of Radiation Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China E-mail :
Asian Pac J Cancer Prev. 2013;14(11):6321-6. doi: 10.7314/apjcp.2013.14.11.6321.
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.
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.
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.
FBW7 is a potential drug target for combating drug resistance and regulating the EMT in NSCLC cells.
肺癌对人类健康危害极大，在全球所有恶性肿瘤中发病率位居前列。约80%的肺癌被归类为非小细胞肺癌（NSCLC）。以顺铂为基础的多药化疗方案是此类病变的标准治疗方法，但耐药性问题日益突出。含F-box/ WD重复序列蛋白7（FBW7）是F-box蛋白家族成员，可调节细胞周期进程、细胞生长和分化。FBW7还具有肿瘤抑制功能。
我们使用细胞活力测定、蛋白质免疫印迹法以及免疫荧光法，并结合小干扰RNA（siRNA）干扰或质粒转染，来研究NSCLC细胞中顺铂耐药的潜在机制。
我们发现FBW7上调显著增加顺铂化疗敏感性，且表达低水平FBW7的细胞（如NCI-H1299细胞）具有间充质表型。此外，siRNA介导的FBW7沉默或质粒介导的FBW7上调导致NSCLC细胞上皮-间充质转化（EMT）模式改变。这些数据支持FBW7在调节NSCLC细胞EMT中的作用。
FBW7是对抗NSCLC细胞耐药性和调节EMT的潜在药物靶点。
