Inhibitory effect of YC-1 on induction of VEGF and GPI genes in hypoxic human pancreatic cancer cells.
- Author:
Jing DU
1
;
Qiu ZHAO
;
Hua GU
;
Xiao-Li TENG
;
Hua QIN
;
Nan-Zhi LIU
Author Information
- Publication Type:Journal Article
- MeSH: Blotting, Western; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; drug effects; Enzyme Activators; pharmacology; Gene Expression Regulation, Neoplastic; drug effects; Glucose-6-Phosphate Isomerase; genetics; metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; metabolism; Indazoles; pharmacology; Pancreatic Neoplasms; metabolism; pathology; RNA, Messenger; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; drug effects; Vascular Endothelial Growth Factors; genetics; metabolism
- From: Chinese Journal of Oncology 2006;28(7):486-489
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the function and mechanism of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) on activity of VEGF and GPI genes in human pancreatic cancer PC-3 cells incubated under hypoxic conditions.
METHODSHuman pancreatic cancer PC-3 cells were incubated under hypoxic culture conditions. Immunocytochemical staining was used to detect HIF-1alpha protein expression in hypoxic and normoxic PC-3 cells. Semi-quantitative RT-PCR was used to detect the effect of YC-1 on the expression of VEGF and GPI mRNA and HIF-1alpha protein in PC-3 cells. Effect of YC-1 on the expression of HIF-1alpha protein was examined by Western blotting. MTF assay was used to detect proliferation of hypoxicPC-3 cells.
RESULTSHIF-1alpha expression was mainly located in nuclei in hypoxic PC-3 cells. The mRNA synthesis of VEGF and GPI and the protein expression of HIF-1alpha were significantly decreased in the group treated with the highest concentration of YC-1 (100 micromol/L). Compared to placebo, YC-1 inhibited the proliferation of hypoxic PC-3 cells greatly when it was increased to 100 micromol/L.
CONCLUSIONYC-1 inhibited the transcription of VEGF and GPI in hypoxic human pancreatic cancer PC-3 cells. It was induced by down-regulation of HIF-1alpha protein. YC-1 inhibites the proliferation of PC-3 cells exposed to hypoxic conditions.
