Fig. 7
From: Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition
TGFBR1 is a potential target for GATA4-deficient lung cancer. a and b 5000 cells per well seeded in 96-well plates. Cells were treated with SB525334 (2 μM) and/or trametinib (2 μM). CCK8 value were checked 3 days after drug treatment. a For H23 and b for PC9 (n = 3 per group). c SB525334 (10 mg/kg/day) synergizes with trametinib (10 mg/kg/day) to shrink lung tumor in KRASG12D/GATA4-/- mice. MRI image of lung of pre-treatment (left panel) and post-treatment (middle panel) of lung cancer bearing mice (PreRx and PostRx); β-Galactosidase staining of lung section of post-treatment mice (right panel). Scale = 100 μm. d Statistics of lung tumor burdens recorded in MRI (n = 4 per group). e Statistics of senescence in tumor shown (c) (n = 4 per group). f, g, h and i The tumor sizes and weights of PDX tumors treated with TGFBR inhibitor (SB525334, 10 mg/kg/day), Cisplatin (5 mg/kg, once a week), or combination. SH3166: GATA4-low PDX; SH3a: GATA4-high PDX (n = 6 per group). j Model of how GATA4 regulate TGF-β2 and Wnt-7b signaling and cellular senescence. See text for details. Bars are represented as mean ± SEM of the indicated number (n) of repeats. *P < 0.05, **P < 0.01, and ***P < 0.001 by Student’s t-test
