Fig. 1: Cisplatin treatment induces MAST1 in preclinical and clinical patient tumors.

a Development of cisplatin-resistant model in vivo. KB-3-1 xenograft mice were treated with 2 doses of cisplatin (0.5 and 5 mg/kg/i.p. on day 5 and 10). Tumor volumes (top) and cisplatin resistance of three representative xenograft tumors was determined by cisplatin IC₅₀ at the experimental endpoint (bottom). b Transcriptomic analysis of xenograft tumors collected from mice treated with PBS or cisplatin. RNA-sequencing data are presented as a volcano plot and kinase genes are highlighted in red. c A heatmap and hierarchical clustering analysis summarizing expression profile of kinase genes with a fold change greater than 1.2. MAST1 is highlighted with an arrow. d Quantitative RT-PCR and western blot results show increased MAST1 expression in KB-3-1 xenograft mice tumors collected from the cisplatin-treated group (T1–T3) compared to the vehicle-treated group (V1–V3). Three representative tumors from each group were randomly selected for analyses. e The mRNA and protein levels of MAST1 in KB-3-1 and A2780 cells treated with cisplatin (0.5 μg/ml) for the indicated times were determined as d. f IHC staining scores of MAST1 in paired primary head and neck squamous cell carcinoma (HSNCC) patient tumors obtained before and after platinum therapy. Patients were considered non-responders to platinum treatment when disease recurred within 2 years after chemotherapy. Weighted index (WI) = positive staining (%) x intensity score (0–3 + ). g Representative images of f are shown. Scale bars represent 10 mm for a and 50 μm for g. Data are mean ± SEM for tumor volume in a upper panel (n = 9 mice/group) and mean ± SD for cisplatin IC₅₀ in a lower panel (n = 3 randomly selected tumors/group). For d and e, data are mean ± SD from three independent biological experiments. Statistical analyses were performed by two-way ANOVA for tumor volume and unpaired two-tailed t-test for IC₅₀ in a and d, one-way ANOVA for e, and paired two-tailed t-test for f. Source data are provided as a Source Data file.