Fig. 8: Lestaurtinib suppresses dexamethasone-mediated GR-MAST1 activation and cisplatin resistance while not affecting the anti-inflammatory property of dexamethasone.

a Effect of lestaurtinib on cell viability and MAPK activity of dexamethasone and cisplatin co-treated KB-3-1 and A2780 cells. Cells were treated with 100 nM lestaurtinib, 500 nM dexamethasone, and 3 μg/ml cisplatin. b Effect of lestaurtinib on growth of ovarian cancer patient-derived xenograft tumor organoid treated with cisplatin and dexamethasone. Images (left) and cisplatin IC₅₀ (right) of organoids are shown. Single cell suspended organoids were used for IC₅₀ analysis. Scale bars represent 100 μm. c, d Effect of lestaurtinib on tumor growth of HNSCC (c) and ovarian cancer (d) PDX mice receiving cisplatin and dexamethasone treatment. Cisplatin (5 mg/kg i.p. twice/week), dexamethasone (0.1 mg/kg i.p. twice/week) and lestaurtinib (20 mg/kg s.c. daily) were treated. Tumor volume (left), tumor weight (right), and Ki-67 IHC staining of PDX tumors (bottom) are shown for HNSCC and ovarian PDX models. Scale bars represent 5 mm for tumor images and 50 μm for Ki-67 staining. e, f Effect of lestaurtinib on tumor growth and inflammation of ID8-luc syngeneic mice receiving cisplatin and dexamethasone treatment. Syngeneic mice were treated as PDX mice. Average photonic flux and BLI (e) and plasma inflammation related cytokine profile (f) from 10 mice/group at week 8 are shown. Data are mean ± SD from three independent biological replicates for a and b. In vivo data are from 8 mice for c, 9 mice for d, 10 mice for e and f. Data are mean ± SEM for tumor volume (left panels in c and d) and SD for tumor weight (right panels in c and d), photonic flux (e), and cytokine profiling (f). Statistical analyses were performed by two-way ANOVA for tumor volume and one-way ANOVA for the rest. Source data are provided as a Source Data file.