Figure 2.
mTOR1/2 inhibition is synergistic in melanoma cell lines with de novo resistance to selumetinib and elevated OxPhos. (A) Scatter plot of basal OxPhos (OCR) and PGC1α transcript levels in a panel of 14 selumetinib-resistant melanoma cell lines that are BRAF-mutant (orange), NRAS-mutant (red), or BRAF/NRAS wild-type (blue). (B) Scatter plot showing correlation of the combination index (CI) of selumetinib and AZD8055 with basal OCR in the cell lines. CI < 1.0 indicates synergistic inhibition of cell proliferation by the combination. (C) Box plot showing of PGC1α expression in cell lines with CI>1.0 (Red) and CI<1.0 (Green) for selumetinib+AZD8055. (D) Sub-G1 cell populations detected by FACS following 72 h of the indicated treatments. The BRAF (“*”) mutant and NRAS (“**”) mutant cells were treated with 0.25μM of the inhibitors (alone and in combination). Data is average of 3 replicates; error bars, standard deviation.