Therapeutic
targeting of CSCs in colorectal tumor spheroids. Heatmap
plots in (a,b) represent fraction of cells affected (Fa) by single-agent
and combination treatments (trametinib and mithramycin) and the respective
combination index values corresponding to the combined concentrations
of the two compounds. (c) Gene expression analysis of HCT116 tumor
spheroids following cyclic treatments with trametinib/mithramycin
combination for (c) CSC genes, (d) STAT pathway (Stat6), Wnt pathway
(axin1 and β-catenin), EMT (E47 and Zeb1), and (e) PI3K/Akt
pathway. All fold change values are relative to nontreated tumor samples.
* denotes p < 0.05 compared to nontreated spheroids.
Error bars represent standard errors from the mean (n = 2 independent experiments, two replicates/experiment).