Fig. 5
(S)-crizotinib inhibits NCI-H460 xenograft growth in vivo. a Tumor volume in vehicle and (S)-crizotinib treated mice. NCI-H460 cells were injected in the flanks of nude mice and tumors were allowed to develop for 6 d (50–100 mm3). Mice bearing NCI-H460 xenografts then received (S)-crizotinib at 7.5 or 15 mg/kg interperitoneally. Tumor volumes were calculated as described in the methods section. [*P < 0.05 and **P < 0.01]. b Images of resected tumor tissues at day 16. c Tumor weights at the end of the treatment period (16 d) [*P < 0.05, **P < 0.01 compared to vehicle control]. d Body weight of the mice in vehicle- and (S)-crizotinib-treatment groups. e H&E staining of heart, liver, and kidney specimens from mice harboring NCI-H460 tumor [magnification 20×]. f Fluorescence images of tumor specimens stained with DHE (red, upper panel) and DCFH-DA (green, lower panel). Tissue sections were counterstained with DAPI (blue). g Levels of MDA in tumor lysates [*p < 0.05 compared to vehicle control]. h Western blot analysis of ATF4, CHOP, and cleaved caspase-3 levels in resected tumor specimens. GAPDH was used as loading control. i Immunohistochemical staining of tumor sections for cell proliferation marker (Ki-67), apoptosis marker (cleaved caspase-3), and ER stress marker phosphorylated eIF2a. Representative images are shown