Mechanism of Arsenic Trioxide Inhibiting Angiogenesis in Multiple Myeloma

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 26; no. 1; pp. 43 - 46
• Main Author: 王雅丹 胡豫 孙春艳 张小平 何文娟
• Format: Journal Article
• Language: English
• Published: China Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430022, China 2006
• Subjects: Angiogenesis Inhibitors - pharmacology; Arsenicals - pharmacology; Brain-Derived Neurotrophic Factor - biosynthesis; Brain-Derived Neurotrophic Factor - genetics; Cell Line, Tumor; Dose-Response Relationship, Drug; Endothelial Cells - cytology; Endothelial Cells - metabolism; Humans; Multiple Myeloma - blood supply; Multiple Myeloma - metabolism; Neovascularization, Pathologic; Oxides - pharmacology; Receptor, trkB - biosynthesis; Receptor, trkB - genetics; 三氧化砷; 病理机制; 血管生成; 骨髓瘤; brain derived neurotrophic factor; multiple myeloma; arsenic trioxide; angiogenesis
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/bf02828035

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. 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.