Fig. 2: Modulating LKB1 status alters sensitivity to MAPK + MCL-1 inhibition in vitro and in vivo.
From: LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers
A, B Comparison of relative ∆AUC for isogenic LKB1-proficient and deficient KRAS-mutant cell line pairs (EV—empty vector, LKB1—LKB1 expression vector, sgGFP or LKB1—CRISPR KO of GFP or LKB1). Each dot represents an independent biological replicate (N = 3-6). For Sotorasib, H2030: **p = 0.002, H2122: *p = 0.012, MGH1112-1: *p = 0.014, MGH1114-1: *p = 0.037, H358: **p = 0.007. For Trametinib, H2030: **p = 0.003, H2122: *p = 0.026, H23: **p = 0.002, A549: *p = 0.007, MGH1114-1: *p = 0.011, MGH1112-1: *p = 0.015, H358: **p = 0.0014, H441: ***p = 0.0005, SW1573: **p = 0.002. Paired-parametric t test, 2-sided. Apoptotic response of isogenic KRAS-mutant NSCLC cell lines after treatment with 0.1 µM trametinib or 1 µM sotorasib in combination with 1 µM of AMG 176 (annexin positivity assessed by flow cytometry (C) or live-cell imaging (D). C Each dot represents an independent biological replicate, N = 3-5, H23: **p = 0.003, MGH1112: *p = 0.015, H2030: **p = 0.0017, MGH9019-2: *p = 0.011, SW1573: ****p = 0.00001, H358: ****p = 0.000015, unpaired-nonparametric t test, two-sided. D data are mean and S.E.M. of 3 technical replicates. E Subcutaneous xenograft tumors were established from H2030 EV and H2030 LKB1 cell lines, and mice were treated with vehicle, sotorasib (30 mg/kg daily), trametinib (3 mg/kg daily), AMG 176 (50 mg/kg daily) or combination. Data shown are mean and S.E.M of N = 5-6 mice per arm, statistical difference between single agent and combination arms was determined using mixed 2-way ANOVA effects model, *p = 0.01, **p = 0.0084. Source data are provided as a Source Data file.
