Mechanisms of arsenic trioxide inhibiting angiogenesis in multiple myeloma

Abstract

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 assayin 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. As₂O₃ depressed the expression of BDNF and TrkB in the dose- and time-dependent manner. As₂O₃ 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. As₂O₃ 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 As₂O₃ treating MM via the inhibition of angiogenesis.

Keywords

arsenic trioxide / brain derived neurotrophic factor / multiple myeloma / angiogenesis

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