Figure 1
From: Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma
Inhibitory effect of PRi and MEKi combination on cell growth of NRAS mutant melanoma cell lines, and effects of the combination therapy on cell cycle progression. A) Four examples of growth inhibition assays performed on NRAS mutant melanoma cell lines. M207 and M311 are examples of cell lines resistant to both drugs and their combination. M243 and M296 cell lines are examples of cell lines with high synergistic effect of combination therapy. B) Bar graph of IC50s of PRi and MEKi alone or in combination. Cell lines were treated with serial dilutions of the drugs starting from the highest concentration of 10000 nM for PRi and 1000 nM for MEKi. The ratio of PRi to MEKi concentration was constant at 10:1. Cell lines are aligned in the graph according to their IC50s (in pM) of the combination treatment. C) Combination of PRi and MEKi shows synergistic effects in most of the tested NRAS mutant cell lines. Combination Indices (CI) at IC75 were calculated by CalcuSyn software as indicators of the synergistic effect of PRi and MEKi combination. Cell line are divided into three groups (intermittent lines), highly synergistic (CI ≤ 0.1), synergistic (0.28 < CI < 0.39) and antagonistic (CI > 1.0). D) Three resistant cell lines (M202, M207, M311) and three sensitive cell lines (M243, M296, SKMEL173) were treated with PRi (500 nM), MEKi (25 nM) and their combination for 48 hours. After harvest and fixation, samples were stained with DAPI for cell cycle analysis by flow cytometry. R = Resistant cell line, S = Sensitive cell line.