Abstract:OBJECTIVE: To investigate the effect of vascular endothelial growth factor (VEGF) on the apoptosis of human acute leukemia HL-60 cell line and to analyze the role of the related apoptosis genes, such as Bcl-2 and Mcl-1, in the process of apoptosis of human acute leukemia cells. METHODS: HL-60 cells were treated with different concentrations of VEGF (2 μg/L, 20 μg/L or 100 μg/L ) or 20 mg/L of etoposide (VP16, an apoptosis inducter) alone or VEGF plus VP16. After 18 hrs of treatment, the apoptosis rate of HL-60 cells was detected by single-cell gel electrophoresis and flow cytometry. The expressions of Bcl-2 and Mcl-1 of HL-60 cells were detected by RT-PCR. The Control group did not receive any treatment. Immunocytochemistry was used to detect the VEGF and Mcl-1 protein in bone marrow cells from 8 patients with newly diagnosed or relapsed leukemia, 14 leukemia patients in complete remission, and from 5 normal children. RESULTS: Different concentrations of VEGF markedly inhibited the apoptosis of HL-60 cells and decreased the apoptosis induced by VP16 exposure. The Bcl-2 and Mcl-1 mRNA and protein in HL-60 cells treated with VEGF were significantly higher than those in the Control group. The expressions of VEGF and Mcl-1 protein in bone marrow cells of the newly diagnosed and relapsed patients were significantly higher than in patients in complete remission. CONCLUSIONS: VEGF can inhibit the apoptosis of HL-60 cells possibly through increasing the expressions of Bcl-2 and Mcl-1 mRNA and protein, which may represent one of the mechanisms responsible for human acute leukemia. The expressions of VEGF, Bcl-2 and Mcl-1 might be used as the markers for the prognostic evaluation of leukemia.
