[Effect of vascular endothelial growth factor on apoptosis and expression of Bcl-2 and Mcl-1 in acute leukemia cells].
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 microg/L, 20 microg/L or 100 microg/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.
Liao
Xue-Lian
XL
Department of Pediatrics, Tongji Hospital, Tongji University, Shanghai 200065, China. liaoxuelian@sohu.com
Xie
Xiao-Tian
XT
Li
Ben-Shang
BS
Li
Li
L
Yang
Li-Li
LL
D017209:Apoptosis / Q000187:drug effects*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A