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


CONCLUSIONS
Our data indicated GC7 enhances cisplatin cytotoxicity and prevents the EMT in NSCLC cells by inhibiting eIF5A-2.
Guodong
G
Xu
Hui
H
Yu
Xinbao
X
Shi
Lebo
L
Sun
Qingyun
Q
Zhou
Dawei
D
Zheng
Huoshun
H
Shi
Ni
N
Li
Xianning
X
Zhang
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. guofengshaolihuili@163.com.
Guofeng
G
Shao
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D020868:Gene Silencing; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014746:Vimentin / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
D000970:Antineoplastic Agents; D015820:Cadherins; D002945:Cisplatin; D004791:Enzyme Inhibitors; D006147:Guanine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014746:Vimentin; D000097574:Eukaryotic Translation Initiation Factor 5A; C100667:N(1)-guanyl-1,7-diaminoheptane; C063507:deoxyhypusine synthase