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. Author manuscript; available in PMC: 2018 Mar 1.
Published in final edited form as: Cancer Discov. 2017 Jan 20;7(3):302–321. doi: 10.1158/2159-8290.CD-16-0653

Figure 6.

Figure 6

MEK inhibition and BET bromodomain inhibition synergy in vivo. (A) Tumor volume in SUM-159PT xenografts: vehicle, 2 mg/kg daily trametinib, 30 mg/kg daily I-BET151, or combination treatment. Percent change in tumor volume from T11 (B) or 2225 (C) orthotopic serial transplant (OST) models following 2 week treatment of 1.0 mg/kg (chow) trametinib, 30 mg/kg (3X weekly, IP) I-BET151, or the combination. Error bars show +/− SEM. (D) Trametinib-induced mRNA upregulation and I-BET151-mediated suppression of DDR1 and PDGFRB as assayed from total RNA (left) or riboTRAP RNA (right) isolated from SUM-159PT xenografts (n=3). Error bars show SD from mean. (E) Top: SUM-159PT xenograft mean (n=3) transcriptome showing percentage of genes induced (red) or suppressed (green) > 1.5 fold by trametinib treatment. Bottom: Percentage of trametinib-induced genes further induced (red) or suppressed (green) > 1.5 fold by co-treatment with 300 nM JQ1. (F) mRNA fold change of SUM-159PT xenograft tyrosine kinases induced > 1.5 fold by trametinib treatment and corresponding JQ1-mediated suppression. Data are mean +/− SD, n=3 tumors.

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