Figure 1.

Repurposing of mebendazole for chemoresistant hepatoblastoma. (A) Alpha-fetoprotein (AFP) levels in the serum of patients were measured at diagnosis (D) and after the second cycle of chemotherapy (2nd) and are given as log10 ng/mL. Responsiveness to chemotherapy was considered as a decline in AFP level log10 ≥ 1. RNA sequencing data from the 2 non-responders and the 5 responders were retrieved from the Gene Expression Omnibus and differentially expressed genes integrated into Connectivity Map (CMap). The graph shows candidate drugs predicted by CMap with a negative connectivity score indicative of a potential therapeutic value. (B) MTT-based viability assays displaying the response of 5 liver cancer cell lines and 7 PDX cell lines towards mebendazole exposure with 7 increasing concentrations ranging from 0.00128–20 µM. Error bars represent standard error of the mean (±SEM) of three independent experiments, each consisting of two replicates. (C) Heatmaps displaying the proportions of cell viability upon exposure towards increasing concentrations (given in nM) of cisplatin, mebendazole, and doxorubicin in a two-drug combination matrix format (n = 2, duplicates). (D) Three-dimensional synergy landscapes shown separately for each two-drug combination of cisplatin, mebendazole, and doxorubicin, as calculated from cell viability assays (n = 2, duplicates). Maximum synergy scores (MSS) were calculated via Synergyfinder2.0 software with the HSA model.