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ABSTRACT: 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.
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-1alpha 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-1alpha, 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.
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 micromol/L, the expression location of HIF-alpha shifted from nucleus to cytoplasm. Western blotting revealed that YC-1 reduced the level of HIF-1alpha 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.
YC-1 inhibits HIF-1alpha expression in hypoxic pancreatic cancer cells, which is accompanied by the translocation of HIF-1alpha 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.
Pancreas 04/2007; 34(2):242-7. · 2.39 Impact Factor
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 09/2006; 14(8):607-9.
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ABSTRACT: 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.
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.
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.
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.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 08/2006; 28(7):486-9.
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ABSTRACT: To investigate the expression and significance of HIF1 alpha in hepatocellular carcinoma (HCC) tissues and in hepatoma carcinoma cell line HepG2.
The expression of the HIF1 alpha mRNA and protein were detected with immunohistochemistry (IHC), Western blot and RT-PCR techniques in HCC, normal liver tissues and HepG2. Their relationship with the pathological characteristics of the HCC was also analyzed.
HIF1 alpha protein was obviously expressed in HCC. The positive rate of HIF1 alpha protein in HCC tissues was 76.4% and was higher than that in normal hepatic tissues. The expression of HIF1 alpha had a correlation to the differentiation degree of HCC tissues and intrahepatic and extrahepatic metastases (P<0.05), but there was no correlation to the existence of portal vein tumor emboli, the status of HBsAg and the prognosis (P<0.05). The results of Western blot and RT-PCR were similar to the results of IHC. The positive rate of HIF1 alpha in HepG2 was 93.6%. The levels of HIF1 alpha protein and mRNA began to increase after being treated two hours with hypoxia or with CoCl(2) (150 micromol/L).
HIF1 alpha protein is obviously expressed in HCC and it is mainly affected by hypoxia. The expression of HIF1 alpha is related to the differentiation of the HCC and its intrahepatic and extrahepatic metastases but has no correlation to the existence of portal vein tumor emboli, the status of HBsAg and the prognosis.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 04/2006; 14(4):281-4.
