Figure 7: RTK inhibition increases effect of BRAF inhibition.
From: Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma
(a) MITFendo_lo cells were exposed to a combination of RTK inhibitors (AXLi R428 (0.3 μM), EGFRi Gefitinib (2 μM) and PDGFRβi Imatinib (1 μM)) and BRAFi PLX4720 (5 μM). After 9 days of combined treatment the remaining cells were stained with crystal violet. (b) Quantification of a, comprising three independent experiments. Values were normalized to untreated control (100%). Error bars represent s.d.; paired t-test was performed for statistical analysis, *P<0.05, **P<0.01, ***P<0.001. (c) PLX4720-resistant melanoma cells and their treatment-naïve counterparts were immunoblotted for AXL, EGFR and PDGFRβ. CDK4 served as a loading control. (d) PLX4720-resistant SkMel28 and their naïve counterparts were blotted on a phospho-RTK array. (e) Matched human melanoma biopsies obtained from a patient before vemurafenib treatment (pre) and after relapse had occurred (post) were stained for MITF and AXL. Scale bars, 100 μm. (f) AXL-expressing PLX4720-resistant melanoma cells were exposed to 0.3 μM of the AXL inhibitor R428 for 9 days and the remaining cells stained with crystal violet.
