Knockdown of IGF2R suppresses proliferation and induces apoptosis in hemangioma cells in vitro and in vivo.
Int J Oncol
; 45(3): 1241-9, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24968760
ABSTRACT
Insulin-like growth factor-II (IGF-II)/IGF2R signaling plays a pivotal role in cell growth, migration and differentiation in many malignancies. An individual with high IGF-II expression levels has a high risk of developing cancer, but IGF2R is often considered to be a tumor suppressor. To date, little has been reported about the role of IGF-II/IGF2R signaling in hemangiomas (HAs). Thus, uncovering the mechanisms of IGF-II/IGF2R signaling is very important to understanding the development of HAs. In the present study, the expression of IGF-II and IGF2R was investigated in 27 cases of HAs of different phases by immunohistochemistry. Through lentivirus-mediated IGF2R siRNA (Lv-siIGF2R) in HA-derived endothelial cells (HDECs), we observed the effects of IGF2R knockdown on the biological behavior of HA cells. We found that the expression of IGF-II and IGF2R was significantly increased in proliferating phase HAs, but decreased in involuting phase HAs. Furthermore, knockdown of IGF2R in vitro significantly diminished the proliferative activity and induced apoptosis and cycle arrest with decreased expression of PCNA, Ki-67, Bcl-2, Cyclin D1 and E and increased the expression of Bax in the proliferative phase HAs (HDEC and CRL-2586 EOMA cells). In addition, the tumor volumes in a subcutaneous HDEC nude mouse model treated with Lv-siIGF2R were significantly smaller than those of the control group. Taken together, our findings indicate that the expression of IGF-II and IGF2R is increased in proliferating phase HAs, and knockdown of IGF2R suppresses proliferation and induces apoptosis in HA cells in vitro and in vivo, suggesting that IGF2R may represent a novel therapeutic target for the treatment of human HAs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like II
/
Receptor IGF Tipo 2
/
Apoptose
/
RNA Interferente Pequeno
/
Técnicas de Silenciamento de Genes
/
Hemangioma
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article