Figure 1

PDGFR inhibitors block proliferation of CAFs without inducing cell death. A, CAFs from two lung adenocarcinomas were cultivated as described [27] and incubated with 160 different kinase inhibitors (1 μM each). After 48 hours the efficacy of the inhibitors was monitored by MTT. Points represent mean values from two experiments (relative to DMSO-treated controls). Red points represent growth reduction >50% in both strains. B, Left panel: MTT experiments performed with indicated inhibitor concentrations. Data represent mean ± SEM from 37 (Dasatinib, Imatinib), 21 (Nilotinib), 7 (Sorafenib), and 10 CAF strains (Erlotinib). Experiments were performed in triplicates. Right panel: MTT experiments with one concentration representing Cmax. Statistics was performed using unpaired students t-test (*: p < 0.05). C, Proliferation analyzed by BrdU labelling and PI staining. Left panel: representative experiment. Middle panel: percentages of cells in G0/G1, S, and G2/M from CAFs incubated with/without Imatinib (3 μM) or Dasatinib (0.1 μM) for 24 hours (mean ± SEM from 11 strains. Statistics was performed with paired student's t-test; ***: p < 0.001). Right panel: Annexin V staining of CAFs following Imatinib or Dasatinib for 24 hours (mean ± SEM from 11 strains). D, CAFs were stained for β-galactosidase 7 days after treatment with 0.1 μM Dasatinib for 48 hours. As a control we used NAFs cultivated for 5 passages (representative examples). E, Proliferation of CAFs following Dasatinib washout. Cells were treated with Dasatinib for 24 hours. Dasatinib was then washed out and cells were cultivated in drug-free medium for indicated times. Samples were analyzed by BrdU labelling and PI staining (representative experiment).