YC-1 exerts inhibitory effects on MDA-MB-468 breast cancer cells by targeting EGFR in vitro and in vivo under normoxic condition / 癌症
Chinese Journal of Cancer
;
(12): 248-256, 2012.
Artigo
em Inglês
| WPRIM
| ID: wpr-295885
ABSTRACT
3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), the hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor, suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic conditions. Our previous studies demonstrated that YC-1 inhibited breast cancer cell proliferation under normoxic conditions. In the current study, we investigated the targets of YC-1 and mechanism of its action in MDA-MB-468 breast cancer cells. In the in vitro experiments, we found that YC-1 significantly inhibited MDA-MB-468 cell proliferation in normoxia and hypoxia. Under normoxic conditions, YC-1 induced apoptosis of MDA-MB-468 cells and blocked cell cycle in the G1 phase, and these effects were possibly related to caspase 8, p21, and p27 expression. RT-PCR and Western blotting results showed that YC-1 primarily inhibited HIF-1α at the mRNA and protein levels under hypoxic conditions, but suppressed the expression of epidermal growth factor receptor(EGFR) at the mRNA and protein levels under normoxic conditions. In vivo, YC-1 prolonged survival, increased survival rate, decreased tumor size and metastasis rate, and inhibited tissue EGFR and HIF-1α expression. However, YC-1 exerted no obvious effect on body weight. These results indicate that YC-1 inhibits the proliferation of MDA-MB-468 cells by acting on multiple targets with minimal side effects. Thus, YC-1 is a promising target drug for breast cancer.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Oxigênio
/
Patologia
/
Farmacologia
/
Neoplasias da Mama
/
RNA Mensageiro
/
Ciclo Celular
/
Fase G1
/
Apoptose
/
Linhagem Celular Tumoral
/
Carga Tumoral
Limite:
Animais
/
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Chinese Journal of Cancer
Ano de publicação:
2012
Tipo de documento:
Artigo
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