FIGURE 3:
Effects of small-molecule inhibitors on the growth of MCF-7 and MDA-MB-231 cells in 3D rBM cultures. (a) MCF-7 CXCR4WT, MCF-7 CXCR4ΔCTD, and MDA-MB-231 cells were seeded for 2 d and then incubated for 8 d in 3D rBM cultures in the presence of control (DMSO), the MEK1 inhibitor PD98059 (20 μM), the MEK1/2 inhibitor U0126 (10 μM), the CXCR4 inhibitor AMD3100 (40 μM), or the PI3K inhibitor Ly294002 (4 μM). Bars, 150 μm. (b) MCF-7 CXCR4WT, MCF-7 CXCR4ΔCTD, and MDA-MB-231 cells were incubated for 8 d in 3D rBM cultures in the presence of control (DMSO), PD98059 (10 μM) and AMD3100 (20 μM), or U0126 (10 μM) and AMD3100 (20 μM). Cell lines were treated with inhibitors on day 2, and inhibitors were then added to the medium on alternate days. Phase contrast images. Bars, 150 μm. (c) MCF-7 CXCR4WT, MCF-7 CXCR4ΔCTD, and MDA-MB-231 cells were incubated for 8 d in 3D rBM cultures in the presence of control (DMSO), Ly294002 (2 μM) and PD98059 (10 μM), Ly294002 (2 μM) and U0126 (10 μM), or Ly294002 (2 μM) and AMD3100 (20 μM). Cell lines were treated with inhibitors on day 2, and inhibitors were then added to the medium on alternate days. Phase contrast images. Bars, 150 μm. (d) Schematic overview of pathway inhibition.