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. 2021 Apr 13;43(2):457–469. doi: 10.1038/s41401-021-00643-2

Fig. 6. Idelalisib treatment induces feedback activation of the MAPK pathway and upstream RTKs, which was blocked by A-485 via a decrease in histone acetylation at RTK promoters.

Fig. 6

a Pathway phosphorylation changes. Z-138 cells were treated with 1 μM of idela with or without 3 μM of A-485 for the indicated times. Phosphorylation changes in ERK-RSK-mTOR signaling molecules were detected by immunoblotting. Hsp90 was used as the control. b, c RT-qPCR was conducted to measure the mRNA levels of EPHA2 and ERBB2. Z-138 and Maver-1 cells treated with 1 μM of idelalisib at multiple time points for up to 24 h were compared with DMSO-treated control cells. The error bars indicate the SD of three independent experiments. **P < 0.01. d, e Histone acetylation at the EPHA2 and ERBB2 gene promoters. Z-138 cells were treated for 24 h with 1 μM or 3 μM A-485, harvested, and subjected to a ChIP assay using the anti-ac-H3K27 antibody and qPCR analysis using primers targeting the promoter regions of the indicated genes. f A schematic representation of signaling responses to combined inhibition of PI3K and p300/CBP.