Figure 4. SEL-DEX modulates the expression of GR regulated genes.

MM.1S (GR^wt) and MM.1R (GR^null) cells were treated with 200 nM selinexor and 100 nM DEX for 24 hours. (A) The mRNA expression of the related genes was evaluated by real time PCR. DEX treatment alone induced the expression of all target genes to varying degrees in MM.1S cells, while having no effect on MM.1R cells. The combination with selinexor synergistically enhanced the expression of REDD1 in MM.1S cells. (B) The protein levels of GR regulated targets of mTOR activity was evaluated by western blotting. In MM.1S, BCAT2 and REDD1, both downstream of KLF15 (a GR target) exhibited combinatorial increases. In MM.1R, BCAT2 was significantly induced by selinexor treatment, although induction was not enhanced after adding DEX. RHEB expression was significantly reduced by the combination and selinexor in MM.1S and MM.1R respectively.