Journal
PANCREAS
Volume 34, Issue 2, Pages 242-247Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.mpa.0000250135.95144.b6
Keywords
3-(5 '-hydroxymethyl-2 '-furyl)-1-benzyl indazole; pancreatic cancer; hypoxia-inducible factor 1; proliferative vitality; apoptosis
Categories
Ask authors/readers for more resources
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-1 alpha 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-1 alpha, 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-alpha protein in nucleus compared with the normoxic controls. When the dose of YC-1 was at 100 mu mol/L, the expression location of HIF-alpha shifted from nucleus to cytoplasm. Western blotting revealed that YC-1 reduced the level of HIF-1 alpha 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-1 alpha expression in hypoxic pancrea tic cancer cells, which is accompanied by the translocation of HIF1 alpha. 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available