Sunitinib mesylate inhibits proliferation of human colonic stromal fibroblasts in vitro and in vivo.
J Zhejiang Univ Sci B
; 15(8): 701-12, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-25091988
ABSTRACT
OBJECTIVE:
Cancer stromal fibroblasts are important members of the cancer microenvironment. In this study, we determined the effect of sunitinib, a small molecule tyrosine kinase inhibitor, on the primary human colonic fibroblasts.METHODS:
Cell cycle analysis and cell proliferation assays were performed to evaluate the inhibitory effect of sunitinib in vitro. Western-blot analysis was performed to evaluate variations in the levels of phosphorylated platelet-derived growth factor receptor ß (PDGFR-ß), Akt, and ERK proteins. Co-injection of SW620 cells and colonic fibroblasts in nude mice was employed to test anti-growth efficacy in vivo.RESULTS:
Sunitinib was found to effectively inhibit the growth of primary colonic fibroblasts. Low-dose sunitinib blocked the PDGF-BB-induced cell proliferation and PDGFR-ß signaling. Co-injection of SW620 cells and colonic fibroblasts in nude mice generated greater tumor volumes than single injection of SW620 cells. Sunitinib treatment inhibited the SW620 cell+colonic fibroblast tumor growth more effectively than treatment of 5-fluorouracil.CONCLUSIONS:
Sunitinib mesylate inhibited the proliferation of primary human colonic fibroblasts through target-inhibited PDGFR signaling in vitro and in vivo.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Colo
/
Neoplasias do Colo
/
Indóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
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Male
Idioma:
En
Revista:
J Zhejiang Univ Sci B
Ano de publicação:
2014
Tipo de documento:
Article