Fig. 1. Synergistic antiproliferative effects of combined EGFR blockade with JAK inhibition.
(A) MTT-based proliferation assay in H1975, PC-9R, and H1650 cells treated with the TKI erlotinib (Ti) in combination with the JAKi AZD1480 (Ji). Data are means ± SEM from five replicates in three independent experiments. *P < 0.05; **P < 0.001, versus AZD1480 alone (two-tailed Student’s t test). Below each graph are the representative combination indices (CIs) of erlotinib (TKI) in combination with AZD1480 (JAKi): CI < 0.9 indicates synergy, CI between 0.9 and 1.1 is additive, and CI > 1.1 indicates antagonism. The drug dosage combinations used in the MTT assay are boxed. (B) Western blotting in lysates from H1975, PC-9R, and H1650 cells treated with JAKi (AZD1480, 1 μM), TKI (erlotinib, 0.2 μM), or the combination for 1 hour. Blots are representative of three experiments and are quantified in fig. S1D. (C) Tumor volume tracking in mice bearing xenografts of H1975, PC-9R, or H1650 cells and treated with vehicle (C), AZD1480, erlotinib, or the combination (Ji + Ti) for 12 to 25 days. Doses are provided in Materials and Methods. Data are means ± SEM (n = 5 to 7 mice per group). *P < 0.05, AZD1480 versus the combination (two-tailed Student’s t test).