FOXC2 promotes epithelial–mesenchymal transition and cisplatin resistance of non-small cell lung cancer cells
FOXC2 promotes epithelial–mesenchymal transition and cisplatin resistance of non-small cell lung cancer cells
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DOI：
10.1007/s00280-018-3697-2
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Li Wei
中科院分区：
文献类型：
--
作者：
Yuwen He;Hui Xie;Pengjiu Yu1;Shunjun Jiang;Li Wei
Purpose Platinum-based drugs, particularly cisplatin (DDP), are used in the treatment of non-small cell lung cancer.(NSCLC). However, development of drug resistance remains the major therapeutic barrier in NSCLC..Methods The potential cisplatin resistance-related genes were identified from the global transcriptomes of cisplatin-resistant.A549/DDP cells using microarray analysis. Gain- and loss-of-function assays were performed to analyze the effects of Forkhead.Box Protein C2 (FOXC2) on the in vitro and in vivo sensitivity of NSCLC cells to cisplatin and its possible molecular.mechanisms..Results Using global transcriptome analysis, we found that FOXC2 was one of the most upregulated molecules in A549/.DDP cells compared with A549 cells. We further confirmed that the expression of FOXC2 was significantly increased in.cisplatin-resistant NSCLC tissues. FOXC2 knockdown significantly increased the in vitro and in vivo sensitivity of A549/.DDP cells to cisplatin, whereas overexpression of FOXC2 increased cisplatin resistance in cisplatin-sensitive NSCLC cells..Moreover, we found that FOXC2 promoted cisplatin resistance by induction of epithelial–mesenchymal transition (EMT) in.NSCLC cells. Furthermore, FOXC2 activated the AKT/GSK3β signaling pathway, and then increased the protein expression.of EMT-related transcription factor Snail. Inhibition of AKT or knockdown of Snail reversed FOXC2-induced EMT and.cisplatin resistance of NSCLC cells..Conclusion FOXC2 enhanced cisplatin resistance of NSCLC cells through activating AKT/GSK3β/Snail/EMT signaling.pathway, which may be a potential novel therapeutic target for overcoming drug resistance in human NSCLCs.
