Artesunate inhibiting angiogenesis induced by human myeloma RPMI8226 cells

Abstract

Multiple myeloma (MM) remains an incurable plasma cell disorder to date; therefore, new biologically target-based therapies are in urgent demand. Our previous studies showed that the antimalarial artesunate (ART) possessed anti-myeloma effect by inhibiting proliferation and inducing apoptosis of myeloma cells. The present study evaluated the effect of ART on human myeloma cell-induced angiogenesis and elucidated its mechanism. The human umbilical vein endothelial cells (HUVECs) migration test, aortic sprouting in fibrin gel in vitro and chicken chorioallantoic membrane (CAM) neovascularization in vivo model were used to examine the effect of ART on angiogenesis induced by human myeloma cells. The results showed that ART could inhibit HUVECs migration, even at a lower concentration (3μmol/l, P<0.01, compared with the result of control group), and suppress efficiently the angiogenic ability of myeloma RPMI8226 cells in a dose-dependent pattern (3-12μmol/l, P<0.05). The levels of VEGF and Ang-1 in the conditioned medium (CM) were quantified by enzyme-linked immunosorbent assay (ELISA). The results confirmed that 3μmol/l ART could significantly decrease VEGF and Ang-1 secretion by RPMI8226 cells (P<0.05), which correlated well with the reduction of angiogenesis induced by myeloma RPMI8226 cells. The present study also showed that ART downregulated the expression of VEGF and Ang-1 in RPMI8226 cells and reduced the activation of extracellular signal-regulated kinase 1 (ERK1) as well. Therefore, ART can block ERK1/2 activation, downregulate VEGF and Ang-1 expression and inhibit angiogenesis induced by human multiple myeloma RPMI8226 cells. Combined with our previous published data, results from the present study indicate that ART possesses potential anti-myeloma effect.