Insulin Promotes Proliferative Vitality and Invasive Capability of Pancreatic Cancer Cells via Hypoxia-inducible Factor 1α Pathway  

作　　者：汪理 周伟 勾善淼 王统玲 刘涛 王春友 

机构地区：[1]Department of Pancreatic Surgery,Union Hospital,Huazhong University of Science and Technology

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2010年第3期349-353,共5页华中科技大学学报（医学英德文版）

基　　金：supported by a grant from the National Natural Sciences Foundation of China (No.30801098)

摘　　要：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 100 μmol/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-1α protein.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 100 μmol/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-1α protein.

关 键 词：pancreatic cancer cell HIF-1α YC-1 tumor microenvironment proliferation INVASION 

分 类 号：R735.9[医药卫生—肿瘤]