Fig. 1
SKF83566 is a potential therapeutic agent for targeting malignant human glioma. (A) Schematic representation of the brain organoid and GBM spheroid co-culture ex-vivo model, and the heat maps obtained through ultra-low input RNA sequencing analysis and identification of a 27 invasion-related gene signature (Venn Diagram). Analysis of these genes by the CMap database yielded SKF83566 as a potential drug targeting their expression. (B) Cell viability of four GBM cell lines (U251, LN18, LN229, and A172), three human GSCs (P3, BG5 and BG7) and NHA cells following SKF83566 treatment using the CellTiter-Glo assay. Data are shown as the mean ± SEM. Statistical significance was determined with the two-way ANOVA. NHA compared with each cell line and each GSCs, with p-values all less than 0.001. (C) IC50 values following SKF83566 treatment for the 8 cell types. (D) Extreme limiting dilution assay performed with P3, BG5 and BG7 human GSCs. (E)Representative images from tumorsphere formation assays for P3, BG5 and BG7 human GSCs treated with SKF83566. Scale bar = 200 μm. (F) Statistical analysis of tumorsphere formation assays for P3, BG5 and BG7 human GSCs treated with SKF83566 using ANOVA. Data are shown as the mean ± SEM. *** P < 0.001. (G) Western blot analysis of caspase-7, CDK4, PCNA levels in GBM patient derived P3, BG5, and BG7 human GSCs treated with SKF83566