Effects of YC-1 on Hypoxia-Inducible Factor 1-Driven Transcription Activity, Cell Proliferative Vitality, and Apoptosis in Hypoxic Human Pancreatic Cancer Cells


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Abstract

Objectives:To investigate the effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1) on HIF-1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells.Methods:Human pancreatic cancer PC-3 cells were incubated under normoxic or hypoxic conditions. YC-1 was added to the media with different concentrations. The HIF-1α protein expression was detected by means of immunocytochemical staining and Western blotting. Semiquantitative reverse transcriptase polymerase chain reaction was used to determine the mRNA expression of HIF-1α, vascular endothelial growth factor (VEGF), and glucose phosphate isomerase (GPI). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect the cells' proliferative vitality and apoptosis.Results:Hypoxic PC-3 cells expressed a higher level of HIF-α protein in nucleus compared with the normoxic controls. When the dose of YC-1 was at 100 μmol/L, the expression location of HIF-α shifted from nucleus to cytoplasm. Western blotting revealed that YC-1 reduced the level of HIF-1α protein expression, and the inhibitory effect was dose dependent. Moreover, YC-1 dose dependently inhibited mRNA expression levels of VEGF and GPI in hypoxic cells. YC-1 inhibited proliferative vitality and induced apoptosis of hypoxic PC-3 cells in a dose-dependent manner.Conclusions:YC-1 inhibits HIF-1α expression in hypoxic pancreatic cancer cells, which is accompanied by the translocation of HIF-1α from nucleus to cytoplasm, decreased mRNA expression of VEGF and GPI, reduced cell proliferative vitality, and increased apoptosis. These results suggest that HIF-1 is a potential therapeutic target for pancreatic cancer.

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