Fig. 4

Irinotecan shows synergistic activity with INK128 against human malignant peripheral nerve sheath tumor (MPNST) cell lines. a, b Single-drug treatment of human MPNST cell lines with irinotecan or INK128. sNF96.2, ST8814, and STS26T cells were cultured with increasing concentrations of irinotecan (a) or INK128 (b) for 72 h. Cell viability values were determined as mean ± SD percentages of the untreated control value in triplicate experiments. The IC₅₀ values of each cell line in this assay are indicated in parentheses. c–h Normalized isobologram (obtained with Calcusyn software) over a range of irinotecan and INK128 dosage combinations. sNF96.2 cells were cultured with the irinotecan and INK128 combination represented in panel c, and their growth was measured at 72 h. The combination index (CI) was plotted as a function of dose combination, with average CIs for the drug combination reported in panel d. The additive isobole is depicted in this panel as a red straight line, with synergistic dose combinations labeled below the isobole. An average CI of 1 indicates an additive effect, CI < 1 a synergistic effect, and CI > 1 an antagonistic effect. Experiments performed in panels c and d were repeated with ST8814 (e, f) and STS26T (g, h) cells