FIGURE 5 from Activator Protein-1 (AP-1) Signaling Inhibits the Growth of Ewing Sarcoma Cells in Response to DNA Replication Stress

Abstract

<p>HDAC inhibitors decrease the level of the RRM1 protein and increase expression of c-Jun in Ewing sarcoma cells. <b>A,</b> EW8 and TC71 cell lines were treated with the dual PI3K-HDAC inhibitor fimepinostat for 24 hours and then cell lysates were collected for immunoblotting. <b>B,</b> Dose–response curves for Ewing sarcoma cell lines treated with different concentrations of fimepinostat for 72 hours. Cell viability was assessed using the AlamarBlue Fluorescence Assay. The results are representative of two independent experiments. Error bars represent mean ± SD of three technical replicates. <b>C,</b> Ewing sarcoma (EW8 and TC71) and osteosarcoma (U2OS) cell lines were treated with the HDAC inhibitors panobinostat or romidepsin for 24 hours and then cell lysate was collected for immunoblotting. <b>D,</b> log<sub>2</sub> fold change (FC) in RRM1 mRNA in EW8 and TC71 cells treated with panobinostat or romidepsin for 24 hours. The results are representative of two independent experiments. Error bars represent the mean ± SD of three technical replicates. <b>E,</b> EW8 and TC71 cells were treated with panobinostat, romidepsin, or fimepinostat for 24 hours and then cell lysates were collected for immunoblotting. <b>F,</b> Ewing sarcoma cell lines were treated with romidepsin for 24 hours and then cell lysates were collected for immunoblotting.</p>