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.
Cell Physiol Biochem
; 36(6): 2494-503, 2015.
Article
em En
| MEDLINE
| ID: mdl-26279450
ABSTRACT
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.CONCLUSION:
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Doxorrubicina
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Receptores de Estrogênio
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Fatores de Iniciação de Peptídeos
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Proteínas de Ligação a RNA
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Diaminas
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Transição Epitelial-Mesenquimal
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article