Mechanism of arsenic trioxide inhibiting angiogenesis in multiple myeloma.
In order to explore the molecular mechanism of arsenic trioxide treating multiple myeloma (MM) via inhibition of angiogenesis, the expression of brain derived neurotrophic factor (BDNF) and its specific receptor TrkB in human MM cell line KM3 and endothelial cell line ECV304 was detected by Western blotting. The angiogenic activity was evaluated by wound migration assay and tubule formation assay in vitro. The results showed that BDNF was detected in the MM cells and TrkB in the endothelial cells. Furthermore, 100 ng/mL BDNF could significantly induced endothelial cell tubule formation and wound migration. As2 O3 depressed the expression of BDNF and TrkB in the dose- and time-dependent manner. As2 O3 inhibited BDNF-induced wound migration and capillary tube formation. It was concluded that BDNF is a novel angiogenic protein as well as VEGF and has a relation with the pathogenesis of MM. As2 O3 interrupts a paracrine loop between MM cells and endothelial cells by down-regulating the TrkB expression in endothelial cells and inhibiting BDNF production in MM cells, finally resulting in inhibition of MM angiogenesis. This is probably one part of the mechanisms of the As2 O3 treating MM via the inhibition of angiogenesis.
Wang
Yadan
Y
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hu
Yu
Y
Sun
Chunyan
C
Zhang
Xiaoping
X
He
Wenjuan
W
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000098:blood supply* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010087:Oxides / Q000494:pharmacology*; D020813:Receptor, trkB / Q000096:biosynthesis* / Q000235:genetics
D020533:Angiogenesis Inhibitors; D001152:Arsenicals; D019208:Brain-Derived Neurotrophic Factor; D010087:Oxides; D020813:Receptor, trkB; D000077237:Arsenic Trioxide