Insulin promotes proliferative vitality and invasive capability of pancreatic cancer cells via hypoxia-inducible factor 1alpha pathway.
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.
Wang
Li
L
Department of Pancreatic Surgery, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China. huanhuan1229@163.com
Zhou
Wei
W
Gou
Shanmiao
S
Wang
Tongling
T
Liu
Tao
T
Wang
Chunyou
C
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006162:Guanylate Cyclase; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D007328:Insulin; D012333:RNA, Messenger; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D006162:Guanylate Cyclase