The Effect of Ruxolitinib on the Expression of VEGF and HIF-1.ALPHA.in Leukemia HEL Cells

OBJECTIVES: To investigate the effect of Ruxolitinib on the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 α (HIF-1α) in HEL cells. METHODS: he HEL cells were treated with Ruxolitinib in different concentrations (1 nmol/L, 5 nmol/L, 10 nmol/L, 50 nmol/L, 100 nmol/L, 500 nmol/L). The growth inhibition of Ruxolitinib on HEL cells was detected by CCK-8 assay;the mRNA expression level ofJAK2 were measured by RT-PCR and the protein level of p-JAK2, VEGF, HIF-1α were observed by Western blot after treated with Ruxolitinib for 24,48,72 h. Chick chorioallantoic membrane (CAM) test was used to testify the effect of Ruxolitinib on angiogenesis. RESULTS: Ruxolitinib with different concentrations could inhibit HEL cells proliferation. RT-PCR showed that the mRNA level ofJAK2 decreased in a concentration-dependent manner and Western blot demonstrated that the expression levels of p-JAK2, VEGF and HIF-1α were lower in Ruxolitinib treatment groups than those in control group (P<0.05) after HEL cells were treated with different concentrations of Ruxolitinib for 24,48,72 h. Ruxolitinib significantly suppressed blood vessels'formation in CAM. CONCLUSIONS: Ruxolitinib can inhibit VEGF, HIF-1α expression and angiogenesis of HEL leukemia cells by inhibiting JAK2 pathway.