Fig. 7

Combination treatment of ceritinib and paclitaxel (PTX) has robust inhibitory effect on patient derived xenograft (PDX) model. The combination of ceritinib and PTX synergistically suppressed the TU-BcX-4EALNb PDX tumor growth. The tumor volume and body weight were monitored twice a week. The combination of ceritinib and PTX synergistically suppressed the TU-BcX-4EALNb PDX tumor growth. TU-BcX-4EALNb tumors were implanted in 4-5 week-old NSG female mice. Mice were assigned into four groups including untreated control, ceritinib (25 mg/kg bodyweight) alone, PTX alone (10 mg/kg of bodyweight), and ceritinib (25 mg/kg bodyweight) + PTX (10 mg/kg of bodyweight). A, Different tumors; B, tumor volume measured over a period of 28 days; C, body weight measured over a period of 28 days. The data represent mean ± SEM and are ananlyzed by GraphPad prism 8 software. * p < 0.05; ** p < 0.01; *** p < 0.001. D, Ex vivo ceritinib and PTX combination treatment significantly increased the apoptosis in TU-BcX-4EALNb PDX xenograft tumors. The freshly isolated TU-BcX-4EALNb tumor was cut into 2 × 2 mm pieces, the tumor slices were treated with DMSO, 1 μM ceritinib, 10 nM PTX and 1 μM ceritinib + 10 nM PTX for 48 h. The apoptotic proteins were detected by western blot assay, and the downstream signaling proteins p-FAK and p-YB-1 were examined by western blot assays in E