Journal: EMBO Molecular Medicine

Article Title: Repurposing statins and phenothiazines to treat chemoresistant neuroblastoma

doi: 10.1038/s44321-025-00349-6

Figure Lengend Snippet: ( A ) Dose–response curves of the four top hits tested in three PDX-derived high-risk neuroblastoma organoids (LU-NB-1, 2, and 3) for 3 and 7 days, mean percent viability of control ±SD, n = 3. ( B ) Synergy testing between the two drug classes, phenothiazines and statins. Workflow for identifying the final drug pair. Combination total scores of 6 ×6 synergy matrices over 3 or 7 days, SynergyFinder’s MSA score and total efficacy volume (total effect calculated under the whole dose–response matrix), n = 2. ( C ) Synergy landscape of the PCZ + PIT combination tested in LU-NB-1 and LU-NB-2 organoids for 3 and 7 days, average of n = 2. ( D ) Representative photographs of NB organoid size and integrity following single drug and PCZ (1.6 µM) + PIT (2.2 µM) combination treatment (scale bar 100 µm), 7 days. ( E ) Propidium iodide (PI) staining for PCZ (1.6 µM) + PIT (2.2 µM) combination over a 7-day treatment. Bars represent the mean, n = 2 per group. ( F ) Experimental set-up for intratumoral (i.t.) treatment with single drugs and the combination. Subcutaneous LU-NB-1 PDX tumors were established in NSG mice. ( G ) Average tumor volume per group, day 8 (control n = 5, PCZ n = 4, PIT n = 5, combination n = 7, one-way ANOVA followed by Tukey’s multiple comparisons test; boxes represent the interquartile range and whiskers indicate minimum and maximum values). ( H ) Kaplan–Meier curves showing survival in days from the first treatment day. Statistical analysis was performed using the log-rank test between control and combination group. TFP trifluoperazine, TRD thioridazine, PCZ prochlorperazine, LOV lovastatin, PIT pitavastatin, FLV fluvastatin, MSA Most Synergistic Area score, ZIP zero interaction potency score, QD quaque die-once a day. .

Article Snippet: fluvastatin , Selleckchem , S1909.

Techniques: Derivative Assay, Control, Staining