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Inhibitory effect of YC-1 on stability and transcriptional activity of HIF-1 in hypoxic human liver cancer cells-HepG-2

DU Jing1,ZHAO Qiu21.Department of Gastroenterology,Zhejiang Provincial People's Hospital,Hangzhou 310014,P.R.China2.Department of Gastroenterology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,P.R.China  
OBJECTIVE:To investigate the effects of YC-1 on stability and transcriptional activity of HIF-1 in human liver cancer cells-HepG-2 incubated in hypoxic conditions,and to discuss probable mechanism which there is.METHODS:Human liver cancer cells-HepG-2 were incubated under hypoxic culture.Semi-quantitative RT-PCR and Western blotting were used to detect the HIF-1α and its target genes' mRNA and protein levels treated with diverse concentrations of YC-1.MTT assay were used to detect proliferation vitality of hypoxic HepG-2 cells.RESULTS:Comparing to the normoxic controls,for HIF-1α and its target genes,the mRNA levels highly increased in hypoxia,P0.05.Under hypoxic conditions,the mRNA synthesis and protein expressions of those targeted genes decreased progressively after dealt with increasing dose of YC-1(P0.05),and YC-1 seemed to have no effect on the HIF-1α mRNA levels,but it developed a dose-dependent reduction on HIF-1α protein expression.YC-1 inhibited the proliferation of hypoxic HepG-2 cells in a dose-dependent manner.CONCLUSIONS:YC-1 inhibits the stability and transcriptional activity of HIF-1 in a dose dependent-manner in human liver cancer cells-HepG-2 which is incubated in hypoxia.YC-1 inhibits the proliferation of hypoxic HepG-2 cells in a dose-dependent manner.Our study suggests that HIF-1 might become a new potential therapeutic target for human liver cancer.
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