Inhibitory effect of YC-1 on induction of VEGF and GPI genes in hypoxic human pancreatic cancer cells

Objective: To 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.

Methods: Human 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.

Results: HIF-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.

Conclusions: YC-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.