Fig. 5: The detection of intracellular apigenin uptake and validation for multiple chemotherapeutics.
A The determination of intracellular apigenin concentration in WT, KO and 2 mM BAG-pretreated MCF-7 cells. B The detection of intracellular apigenin concentration in plasmids transfected HEK 293 T cells. C IC50 of WT/KO cells treated with different natural compounds for 48 h. D Cell viability of WT/KO cells pretreated with 2 mM BAG for 24 h then 50 μM natural compounds for 48 h. E Calculated IC50 for selected drugs in BRCA and LUSC cell lines, respectively. MUC1 is overexpressed in BRCA, but little expressed in LUSC. F Calculated IC50 of selected drugs in PAAD and SKCM cell lines, respectively. G Cell viability of WT/KO cells treated with selected drugs for 48 h. H Cell viability of WT/KO cells pretreated with 2 mM BAG for 24 h thereafter selected drugs for 48 h. I Correlation between drug sensitivity and mRNA expression of MUC1 and related O-glycosyltransferase genes from CTRP database. Most of these genes were positively (red) correlated with drug tolerance, implying that MUC1 along with over-glycosylation possibly leads to drug resistance. J A proposed model of MUC1 O-glycosylation induced resistance to apigenin treatment. Extensive O-glycosylation on MUC1 N-terminal induces drug resistance and mitigate cellular apoptosis, cell cycle arrest and mitochondrial dysfunction. Each group was analyzed in triplicate. *P < 0.05; **P < 0.01; ***P < 0.001 for comparisons.
