Insulin promotes proliferative vitality and invasive capability of pancreatic cancer cells via hypoxia-inducible factor 1α pathway

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 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.

Keywords

pancreatic cancer cell / HIF-1α / YC-1 / tumor microenvironment / proliferation / invasion

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