Effects of GW654652 on the bone marrow microenvironment. (A-B) GW654652 inhibits the secretion of VEGF and IL-6 induced by MM cell line binding to BMSCs. MM.1S cells were cultured in control media alone or with the indicated concentrations of GW654652. VEGF (A) or IL-6 (B) concentrations were measured using ELISA. (C-D) GW654652 inhibits the secretion of VEGF and IL-6 induced by patient MM cell binding to BMSCs. Patient MM cells were cultured in control media alone or with the indicated concentrations of GW654652. VEGF (C) or IL-6 (D) concentrations were measured using ELISA. (E) GW654652 inhibits proliferation of MM cells adherent to BMSCs. MM cells were cultured with or without BMSCs. GW654652 was added in the indicated concentrations, and proliferation was measured using [³H]-thymidine uptake. (F) Inhibition of HUVEC proliferation in the presence of conditioned medium from a MM-BMSC cell culture. Supernatants derived from MM-BMSC cultures pretreated with GW654652 were mixed with EGM-2MV media. HUVEC cell proliferation was measured using [³H]-thymidine uptake. Experiments were performed in triplicate. Data shown are the mean ± SD of experiments performed in triplicate.