Effect and mechanism of NF-κB on regulation of HIF-1α-VEGF pathway in human non-Hodgkin lymphoma

OBJECTIVE:To investigate the role of NF-κB in regulation of HIF-1α expression of human non-Hodgkin lymphoma(NHL) cells in normoxic condition,as well as to explore the mechanism mediating this effect.METHODS: Expression levels of VEGF protein in three human non-Hodgkin lymphoma cell lines,Namalwa,Ramos,and Raji cell were determined by Western blot after treatment with EC,a HIF-1α antagonist or with pSuper HIF-1α/siRNA transfection.Cells were pre-treated by NF-κB antagonist QNZ and Bay11-7082,then HIF-1α and VEGF protein levels were determined with Western-blot,and expression levels of HIF-1α mRNA were quantified by RT-PCR method.RESULTS: EC significantly reduced the expression level of VEGF(P0.05).The effect of down-regulation of VEGF expressions were also achieved in the three NHL cell lines transfected by pSuper HIF-1α/siRNA(P0.05).At the same time,inhibition of NF-κB significantly reduced HIF-1α protein and mRNA level as well as its related protein VEGF expression of human NHL cell in a dose dependent manner(P0.05).CONCLUSION: The pathway of HIF-1α-VEGF can be inhibited by Inhibition of NF-κB in human NHL cell in normoxic condition through down-regulation transfection of HIF-1α.