Insulin Promotes Proliferative Vitality and Invasive Capability of Pancreatic Cancer Cells via Hypoxia-inducible Factor 1α Pathway
10.1007/s11596-010-0355-2
- Author:
WANG LI
1
;
ZHOU WEI
;
GOU SHANMIAO
;
WANG TONGLING
;
LIU TAO
;
WANG CHUNYOU
Author Information
1. Department of Pancreatic Surgery,Union Hospital,Huazhong University of Science and Technology,Wuhan 430022,China.
- Keywords:
pancreatic cancer cell;
HIF-1α;
YC-1;
tumor microenvironment;
proliferation;
invasion
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2010;30(3):349-353
- CountryChina
- Language:Chinese
-
Abstract:
This study examined whether insulin-stimulated hypoxia-inducible factor 1α(HIF-1α)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-1α)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 100μmol/L).HIF-1α 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-1α protein expression,and YC-1 could dose-dependently block this effect.However,neither insulin nor YC-1 altered HIF-1α 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-1αprotein.
