SNX-2112 inhibits Akt and ERK pathway and overcomes the growth stimulatory effects of IL-6, IGF-1, and BMSCs on MM cell growth. (A) MM.1S, U266, and OPM1 cells were cultured with SNX-2112 (125 nM) for the indicated times. (B) MM.1S cells were cultured with or without SNX-2112 (0-250 nM) for 12 hours and then stimulated with IL-6 (10 ng/mL) or IGF-1 (50 ng/mL) for 10 minutes. Cell lysates were analyzed by Western blotting (A,B). (C) MM.1S cells were cultured for 48 hours with indicated concentrations: 0 nM (□), 5 nM () 10 nM (■) of SNX-2112, in the presence or absence of IL-6 (1 or 10 ng/mL; left) or IGF-1 (10 or 50 ng/mL; right). (D) MM.1S cells were cultured with BMSCs for 48 hours with the indicated concentrations: 0 nM (□), 10 nM (), 20 nM (), 40 nM (■) of SNX-2112. (E) SNX-2112 treatment for 48 hours does not affect cell viability of BMSCs: BMSC-1 (■), BMSC-2 (□), BMSC-3 (▴) (n = 3). Cell growth was assessed by [³H]-thymidine uptake (C,D) and MTT assay (E). Values represent mean plus or minus SD of quadruplicate (C,D) or triplicate cultures (E).