N1-guanyl-1,7-diaminoheptane enhances the chemosensitivity of NSCLC cells to cetuximab through inhibition of eukaryotic translation initiation factor 5A2 activation.
OBJECTIVE
N1-guanyl-1, 7-diaminoheptane (GC7), an inhibitor of deoxyhypusine synthase has been shown to exhibit significant anti-cancer activity. However, the biological role of eukaryotic translation initiation factor 5A2 activation (EIF5A2) and GC7 on drug resistance in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we aimed to investigate the therapeutic effect of GC7 combined with cetuximab in NSCLC therapy.


METHODS
The current study used cell viability assays, EdU incorporation assays, and western blot to detect that the GC7 exhibited synergistic cytotoxicity with cetuximab in NSCLC.


RESULTS
CCK-8 assays showed that combined treatment with GC7 and cetuximab significantly inhibited the viabilities in three NSCLC cell lines. In addition, EdU incorporation assays also indicated that GC7 co-treatment remarkably enhanced the cetuximab sensitivity in NSCLC cells. Nevertheless, down-regulation of EIF5A2 diminished the regulatory role of GC7 in cetuximab cytotoxicity. Western blot showed that transfection of EIF5A2 siRNA significantly suppressed the protein expression of EIF5A2 in NSCLC cells.


CONCLUSIONS
These findings demonstrate that combined treatment with GC7 could enhance cetuximab sensitivity by inhibiting EIF5A2 in NSCLC cells, implying the potential clinical application of GC7 in cetuximab-based chemotherapy for NSCLC patients.
Department of Respiratory Medicine, The First Affiliated Hospital of Huzhou Teachers' College, the First People's Hospital of Huzhou, Huzhou, Zhejiang, China. baoyinghz@sina.com.
X
X
Wang
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Jiang
E-H
EH
Cui
W-M
WM
Feng
H-H
HH
Guo
D-H
DH
Gu
C-W
CW
Tang
T
T
Xue
Y
Y
Bao
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D000068818:Cetuximab / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
D000068818:Cetuximab; D006147:Guanine; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100667:N(1)-guanyl-1,7-diaminoheptane