Figure 4
YOVAL1.1 is responsive to MAPK/ERK pathway-targeted therapy. Response of YOVAL1.1 to BRAF and MEK inhibition (BRAFi and MEKi). (a) Cell proliferation of YOVAL1.1, B16 and A375 cultured in increasing concentrations of PLX4720 (BRAFi) or cobimetinib (MEKi) for 5–6 days. Representative dose response curve shown. GI50s (right panels) were calculated as the concentration of drug leading to 50% growth inhibition. One-way ANOVA, Tukey’s multiple comparisons test, n = 3. (b) YOVAL1.1 or B16 cells cultured with DMSO, 1 μM PLX4720 (BRAFi), 10 nM cobimetinib (MEKi) or BRAFi + MEKi and cell confluency measured every 12–24 hours using IncuCyte®ZOOM. Representative graph of n = 3. (c) Western blot of phospho- and total-ERK (P-ERK and T-ERK) expression in YOVAL1.1, A375 and B16 treated with DMSO, 1 μM PLX4720 (BRAFi), 10 nM cobimetinib (MEKi) or BRAFi + MEKi for 48 hours, representative blot of n = 3. All images were cropped from different parts of the same blot, with exposure times differing according to antibody and cell line (see Supplementary Fig. 7). (d) Tumor growth and survival in YOVAL1.1-bearing C57BL/6 mice treated daily, 6 days/week, with dabrafenib (BRAFi) plus trametinib (MEKi). Survival is measured as time for tumors to reach >1200 mm3, log-rank (Mantel-Cox) test, n = 7. All error bars show ±SEM. ***p < 0.001, ****p < 0.0001.
