Cisplatin sensitivity is enhanced in non-small cell lung cancer cells by regulating epithelial-mesenchymal transition through inhibition of eukaryotic translation initiation factor 5A2

BMC Pulmonary Medicine

Guofeng Shao¹  Xianning Zhang²  Ni Li¹  Huoshun Shi¹  Dawei Zheng¹  Qingyun Zhou¹  Lebo Sun¹  Xinbao Shi¹  Hui Yu³  Guodong Xu¹ 

[1] Department of Thoracic & Cardiovascular Surgery, Lihuili Hospital, Ningbo Medical Center, Affiliated Hospital of Medical School of Ningbo University, NO 57 Xingning Road, Ningbo 315041, China;Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China;Department of Pathology, Shanghai Pulmonary Hospital Tongji University School of Medical, Shanghai 200065, China

关键词: Non-small cell lung cancer (NSCLC);    Cisplatin;    Epithelial-mesenchymal transition (EMT);    Eukaryotic translation initiation factor 5A2 (eIF5A-2);    N1-guanyl-1, 7-diaminoheptane (GC7);   

Others  :  1091459
DOI  :  10.1186/1471-2466-14-174

 received in 2013-07-17, accepted in 2014-10-16,  发布年份 2014

【 摘 要 】

Background

Epithelial-mesenchymal transition (EMT) has been believed to be related with chemotherapy resistance in non-small cell lung cancer (NSCLC). Recent studies have suggested eIF5A-2 may function as a proliferation-related oncogene in tumorigenic processes.

Methods

We used cell viability assays, western blotting, immunofluorescence, transwell-matrigel invasion assay, wound-healing assay combined with GC7 (a novel eIF5A-2 inhibitor) treatment or siRNA interference to investigate the role of eIF5A-2 playing in NSCLC chemotherapy.

Results

We found low concentrations of GC7 have little effect on NSCLC viability, but could enhance cisplatin cytotoxicity in NSCLC cells. GC7 also could reverse mesenchymal phenotype in NCI-H1299 and prevented A549 cells undergoing EMT after TGF-β1 inducement. eIF5A-2 knockdown resulted in EMT inhibition.

Conclusion

Our data indicated GC7 enhances cisplatin cytotoxicity and prevents the EMT in NSCLC cells by inhibiting eIF5A-2.

【 授权许可】

   
2014 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

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