Figure 3 from Combining Brigatinib with mTOR Inhibition to Effectively Treat NF2-SWN–Associated and Sporadic NF2-Deficient Meningiomas

The brigatinib + INK128 combination exhibited synergistic antiproliferative activity in AG-NF2-Men cells. A, Dose–response curves from proliferation assays of AG-NF2-Men cells treated for 3 days with serial dilutions of each indicated drug established a mean IC50 of 1,100 nmol/L for brigatinib and 20 nmol/L for INK128. B, AG-NF2-Men cells were treated for up to 14 days with DMSO or 1 x IC50 of brigatinib or INK128 alone or in combination. Cells were harvested in biological duplicates and counted using a hemocytometer. Solid symbols and error bars for both graphs in (A) and (B) represent the mean + SD from two independent experiments. The open symbols show the percent growth inhibition (A) and cell numbers (B) from each independent experiment. C, AG-NF2-Men (left) and Ben-Men-1 (right) cells were treated in a combinatorial array with brigatinib and INK128, and cell proliferation was measured relative to DMSO control cells designated 100%. Shown above are the proliferation matrices indicating the means + SEs from three (AG-NF2-Men) and two (Ben-Men-1) independent experiments. Loewe additivity synergy score matrices are depicted below. Blue shading denotes drug antagonism, whereas red shading indicates enhanced growth inhibition by the brigatinib + INK128 combination. Loewe scores ≤ −0.1 signify synergistic drug interaction.