FIGURE 6 from Targeting the Clear Cell Sarcoma Oncogenic Driver Fusion Gene <i>EWSR1::ATF1</i> by HDAC Inhibition

<p>BET inhibitors enhance the effect of vorinostat on CCS. <b>A,</b> SU-CCS1 and Hewga-CCS cells were treated for 48 hours with the indicated concentrations of vorinostat in the absence (–) or presence (+) of 300 nmol/L JQ1, and the viable number of cells was estimated using a WST-8 assay (<i>n</i> = 3). The calculated combination index values are shown in the histogram. <b>B,</b> SU-CCS1, and Hewga-CCS cells were treated for 24 hours with the absence (–) or presence (+) of 300 nmol/L vorinostat or JQ1. <i>EWSR1::ATF1</i> mRNA levels in CCS cells were quantified using qRT-PCR (normalized to GAPDH; <i>n</i> = 3). <b>C</b> and <b>D,</b> SU-CCS1 and Hewga-CCS cells were engrafted in nude mice, which were treated with vehicle (controls), or 0.4 mg/kg mivebresib, or 20 mg/kg vorinostat, or both drugs in combination (4 mice/group). Tumor volume (C) and weight (D) of SU-CCS1 and Hewga-CCS tumors during treatment are shown (<i>n</i> = 4). *, <i>P</i> < 0.05; **, <i>P</i> < 0.01 (Student <i>t</i> test).</p>