Fig. 5.
The combination of afatinib and gemcitabine induced synthetic lethality in METN375S mutant lung cancer A. left: CT scan image showing the size of the patient's originating tumor (red line), right: the bronchial placeholder image of the tumor under thoracoscopy; B. Representative staining of HE and Ki67 in primary tissues (patient-3); C. PDO-3 (MET N375S) and PDO-8 (MET WT) were treated with various concentration of Afatinib for 72 h, and the PDOs viability were detected using CTG; D. PDO-3 was treated with a single drug or combination of Afatinib and Gemcitibabine for 72 h, the PDOs viability were detected using CTG; E. Representative bliss synergy score heatmap for three independent experiments is shown. Red, synergy; green, antagonism; white, no effect. Synergyavg = average bliss synergy score. F. PDO-3 was treated with Afatinib (1 μM) and/or gemcitabine (1 μM) for 72 h, indicated proteins expression was analyzed using immunoblot analysis, GAPDH was used as loading control. Full-length blot is shown in the supplementary information, and the gels have been run under the same experimental conditions. G. Cytotoxicity analysis of single drug or combination of Afatinib and Gemcitibabine in mini-PDX model, relative tumor organoid growth was shown; H. The body weight of mice used in G during drug treatment. I-K. Expression of p-MET, p-HER2 and P-ERK were quantified and expressed as mean of total MET, HER2 and ERK ± SD (n = 3). Two-tailed Student's t-test; ∗P < 0.05. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)