Insulin promotes proliferative vitality and invasive capability of pancreatic cancer cells via hypoxia-inducible factor 1alpha pathway.
J Huazhong Univ Sci Technolog Med Sci
; 30(3): 349-53, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20556580
ABSTRACT
This study examined whether insulin-stimulated hypoxia-inducible factor 1alpha (HIF-1alpha) expression plays a crucial role in promoting the proliferative vitality and invasive capability in human pancreatic cancer cells. PANC-1 cells were divided into three groups Control group, insulin group and insulin+YC-1 (a pharmacological inhibitor of HIF-1alpha) group in terms of different treatments. Cells in the insulin group or insulin+YC-1 group were treated with insulin (0.1, 1, 10 and 100 nmol/L) alone or combined with 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, 0.1, 1, 10 and 100 micromol/L). HIF-1alpha mRNA and protein expression in PANC-1 cells was determined by real-time RT-PCR and Western blotting respectively. Cell proliferation and invasion were measured by using growth curve and invasion assay, respectively. Western blot analysis demonstrated that insulin dose-dependently increased the HIF-1alpha protein expression, and YC-1 could dose-dependently block this effect. However, neither insulin nor YC-1 altered HIF-1alpha mRNA levels in PANC-1 cells. Moreover, insulin could enhance the proliferation and invasion of PANC-1 cells, while YC-1 could weaken this effect. It was concluded that the malignant proliferation and local invasion of pancreatic cancer cells may be related to high-insulin microenvironment. The tumor biological behavior change resulting from high-insulin microenvironment may be associated with the increased expression of HIF-1alpha protein.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Proliferação de Células
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Indazóis
/
Insulina
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article