N1-Guanyl-1,7-Diaminoheptane Sensitizes Estrogen Receptor Negative Breast Cancer Cells to Doxorubicin by Preventing Epithelial-Mesenchymal Transition through Inhibition of Eukaryotic Translation Initiation Factor 5A2 Activation.
BACKGROUND
Approximately 30% of breast cancer does not express the estrogen receptor (ER), which is necessary for endocrine-based therapy approaches. Many studies demonstrated that eukaryotic translation initiation factor 5A2 (eIF5A2) serves as a proliferation-related oncogene in tumorigenic processes.


METHODS
The present study used cell viability assays, EdU incorporation assays, western blot, and immunofluorescence to explore whether N1-guanyl-1,7-diaminoheptane (GC7), which inhibits eIF5A2 activation, exerts synergistic cytotoxicity with doxorubicin in breast cancer.


RESULTS
We found that GC7 enhanced doxorubicin cytotoxicity in ER-negative HCC1937 cells but had little effect in ER-positive MCF-7 and Bcap-37 cells. Administration of GC7 reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in ER-negative breast cancer cells. Knockdown of eIF5A2 by siRNA inhibited the doxorubicin-induced EMT in ER-negative HCC1937 cells.


CONCLUSIONS
These data demonstrated that GC7 combination therapy may enhance the therapeutic efficacy of doxorubicin in estrogen negative breast cancer cells by preventing EMT through inhibition of eIF5A2 activation.
Department of General Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Yu
Y
Liu
Rongrong
R
Liu
Peifen
P
Fu
Feiya
F
Du
Yun
Y
Hong
Minya
M
Yao
Xianning
X
Zhang
Shusen
S
Zheng
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003959:Diamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D010448:Peptide Initiation Factors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D000097574:Eukaryotic Translation Initiation Factor 5A
D014408:Biomarkers, Tumor; D003959:Diamines; D004317:Doxorubicin; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D000097574:Eukaryotic Translation Initiation Factor 5A; C015127:1,7-diaminoheptane