230 Chapter 7 the potential contribution of the MR in steroid-induced cytotoxicity. In these steroid sensitive samples, we saw a modest decrease in steroid sensitivity after treatment with RU28318, which was most pronounced in the PDX model albeit not significant (Figure 3B). However, no effects of RU28318 could be seen on expression of glucocorticoid target genes in these steroid treated samples (Supplemental Figure 4A). Figure 2. Hydrocortisone most potent steroid in NR3C1 and NR3C2 overexpressing cells (A), Cell toxicity screening of RehNR3C1 (left) and RehNR3C2 (right) cells with (color) and without (gray-scales) doxycycline induction and after treatment with prednisolone, dexamethasone or hydrocortisone. Steroid sensitivity was determined with an MTT-assay. Data represents biological triplicates, with standard deviations. (B), Cell toxicity screening of doxycycline-induced RehNR3C1 (upper panels) and RehNR3C2 (lower panels) with and without 4µM RU28318 (MR antagonist) treatment in combination with prednisolone, dexamethasone or hydrocortisone. RU28318 treatment in RehNR3C2 cells reversed the acquired steroid sensitivity.
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