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Fig. 4 | Journal of Experimental & Clinical Cancer Research

Fig. 4

From: Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer

Fig. 4

Nintedanib selectively localizes to lysosomes and nintedanib fluorescence is detectable in tumor specimen of treated animals. a Subcellular distribution of 10 μM nintedanib in NCI-H1703, DMS114 and NCI-H520 cells after 1 h drug exposure was analyzed by confocal fluorescence microscopy in the FITC channel. LysoTracker® Red served as marker for the lysosomal compartment. Cell boundaries were imaged in the DIC channel. The arrows indicate regions of distinct drug/LysoTracker® Red spatial overlap. The scalebar indicates 10 μm. b Colocalization of nintedanib and lysosome-derived signals was determined using thresholded Manders’ Colocalization Coefficient (MCC). c-e Representative scatter plots showing nintedanib/LysoTracker® Red pixel intensity correlations in NCI-H1703 (c), DMS114 (d) and NCI-H520 (e) cells derived from confocal micrographs shown in Fig. 4a. f Intratumoral nintedanib in tissue cryosections detected by confocal fluorescence microscopy using the FITC channel. Mice bearing subcutaneous CT26 tumor allografts received a single oral dose of 100 mg nintedanib per kg bodyweight or solvent. 2 h after drug administration, mice were sacrificed and consecutive cryosections of OCT-embedded tumors were generated. DAPI served as nuclear counterstain. The endothelial marker MECA-32 was stained to visualize tumor microvasculature. Representative micrographs of tumors are shown from the experiment performed in duplicates

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