期刊
JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL SCIENCES
卷 30, 期 3, 页码 349-353出版社
SPRINGER
DOI: 10.1007/s11596-010-0355-2
关键词
pancreatic cancer cell; HIF-1 alpha; YC-1; tumor microenvironment; proliferation; invasion
资金
- National Natural Sciences Foundation of China [30801098]
This study examined whether insulin-stimulated hypoxia-inducible factor 1 alpha (HIF-1 alpha) 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-1 alpha) 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 mu mol/L). HIF-1 alpha 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-1 alpha protein expression, and YC-1 could dose-dependently block this effect. However, neither insulin nor YC-1 altered HIF-1 alpha 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-1 alpha protein.
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