Inhibition of platelet-derived growth factor C and their receptors additionally increases doxorubicin effects in triple-negative breast cancer cells.
Eur J Pharmacol
; 895: 173868, 2021 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-33460613
ABSTRACT
Complex of platelet-derived growth factor (PDGF) isoforms and PDGF receptors have important functions in the regulation of growth and survival of various cell types. Herein, it was found that aberrant PDGFC expression is closely associated with survival rates in triple-negative breast cancer (TNBC) patients. In addition, PDGFC expression was identified to be significantly increased in TNBC cells unlike other subtypes such as PDGFA, PDGFB, and PDGFD. Apparently, the effects of specific PDGF receptor (PDGFR) inhibitors such as sunitinib and ponatinib on HCC1806 and Hs578T TNBC cells were investigated. Both inhibitors decreased cell viability in a dose-dependent manner. In addition, the inhibitors completely inhibited cell growth in both the cell lines and decreased the expression of matrix metalloproteinase-1 (MMP-1), one of the metastasis-related genes. Cell migration was also decreased by the inhibitors. Finally, the combined effects of the inhibitors with doxorubicin (DOX) were investigated. The results showed that the combination of two PDGFR inhibitors with DOX inhibited the growth of cells and enhanced the apoptotic cell death more uniformly than DOX. Consequently, it is demonstrated that PDGFR inhibitors, sunitinib and ponatinib hold the potential for effective treatment of TNBC.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piridazinas
/
Factor de Crecimiento Derivado de Plaquetas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Doxorrubicina
/
Linfocinas
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Receptores del Factor de Crecimiento Derivado de Plaquetas
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Neoplasias de la Mama Triple Negativas
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Sunitinib
/
Imidazoles
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2021
Tipo del documento:
Article