Figure 1.

Sorafenib is cytotoxic to multiple myeloma (MM) cell lines including those resistant to conventional drugs and overcomes proliferative effect of BMSCs and human umbilical vein endothelial cells (HUVECs). When MM cell lines were incubated with sorafenib for 48 h, dose-dependent cytotoxic effects were observed as measured using the MTT cell viability assay (a). The IC₅₀ value was around 5 μm for most of the cell lines tested. Sorafenib concentration (μm) is indicated on the X axis and viability (as a percentage of the control) is indicated on the Y axis. Error bars represent one s.d. When MM1.S cells were grown in contact with stromal cells (b) or HUVECs (c), an enhanced proliferation of the MM cells were observed (measured by thymidine uptake), which was completely reversed when incubated with sorafenib. The Y axis represents the thymidine uptake (counts per minute) and the X axis represents the drug concentrations. The concentrations of sorafenib used are indicated in the figure and the duration of incubation with sorafenib was 48 h. When MM1S cells were grown with cytokines (25 ng/ml IL-6, 50 ng/ml VEGF,or 50 ng/ml IGF-1) sorafenib can inhibit the increase in cytokine-induced proliferation as measured by thymidine uptake (d). The concentrations of sorafenib used are indicated in the figure and the time of incubation with sorafenib was 48 h. The Y axis represents the thymidine uptake (counts per minute) and the X axis represents the drug concentrations.