Figure S1.
Trametinib reduces c-MYC expression in human PDAC cells.(A) HPAF-II, Panc 10.05, and PDX220 lysates were blotted for c-MYC, pERK1/2, and ACTB after treatment with the indicated concentrations of trametinib for 48 h (n = 1 for HPAF-II and Panc 10.05, n = 2 for PDX220). (B and C) c-MYCT58A expression mediates T/HCQ resistance in PDAC. The tumor volumes of PDX220 expressing Tet-On c-MYCT58A are shown. Inset depicts representative immunoblot analysis of c-MYC, pERK1/2, ERK1/2, and ACTB in cells before injection into mice. Cells were treated with DMSO (first column), 2 μg/ml Dox, 100 nM trametinib (T), and 20 μM CQ, or the combinations thereof, for 48 h. Tumor-bearing mice were treated with: (1) corn oil (control, n = 6); (2) 625 mg/kg Dox chow (n = 6); (3) 1 mg/kg trametinib and 50 mg/kg CQ (T/CQ, n = 6); or (4) the triple combination of Dox, trametinib, and CQ (D/T/CQ, n = 6), where n equals the number of mice. Tumor volumes were assessed over 33 d and arrows denote start of treatments, including when Dox was started or stopped after treatment initiation. Lines are the mean tumor volumes ± SEM. *, P < 0.01; **, P < 0.005; ***, P < 0.0005 by Student’s two-sided t test. Average mouse weights for each treatment group with xenografted PDX220 Tet-On c-MYCT58A are shown in C. Error bars represent SEM. (D–F) Quantitation of IHC performed on xenografts shown in Fig. 2, taken from three regions of stained tumor sections. ns, not significant; *, P < 0.05; **, P < 0.005; ***, P < 0.0005; ****, P < 0.0001 by two-way ANOVA. (G and H) Mouse weights for each xenografted cell type (G, HPAF-II Tet-On c-MYC; H, PDX220 Tet-On c-MYC) were averaged. Error bars represent SEM. (I and J) Alisertib combined with trametinib reduces c-MYC expression in PANC-1 cells. PANC-1 lysates were blotted for c-MYC and ACTB after treatment with trametinib and/or alisertib for 48 h at the indicated concentrations. Representative blots from two (for I) and five (for J) independent experiments are shown. (K) Mouse weights of xenografted PANC-1 were averaged. Error bars represent SEM. Source data are available for this figure: SourceData FS1.

Trametinib reduces c-MYC expression in human PDAC cells. (A) HPAF-II, Panc 10.05, and PDX220 lysates were blotted for c-MYC, pERK1/2, and ACTB after treatment with the indicated concentrations of trametinib for 48 h (n = 1 for HPAF-II and Panc 10.05, n = 2 for PDX220). (B and C) c-MYCT58A expression mediates T/HCQ resistance in PDAC. The tumor volumes of PDX220 expressing Tet-On c-MYCT58A are shown. Inset depicts representative immunoblot analysis of c-MYC, pERK1/2, ERK1/2, and ACTB in cells before injection into mice. Cells were treated with DMSO (first column), 2 μg/ml Dox, 100 nM trametinib (T), and 20 μM CQ, or the combinations thereof, for 48 h. Tumor-bearing mice were treated with: (1) corn oil (control, n = 6); (2) 625 mg/kg Dox chow (n = 6); (3) 1 mg/kg trametinib and 50 mg/kg CQ (T/CQ, n = 6); or (4) the triple combination of Dox, trametinib, and CQ (D/T/CQ, n = 6), where n equals the number of mice. Tumor volumes were assessed over 33 d and arrows denote start of treatments, including when Dox was started or stopped after treatment initiation. Lines are the mean tumor volumes ± SEM. *, P < 0.01; **, P < 0.005; ***, P < 0.0005 by Student’s two-sided t test. Average mouse weights for each treatment group with xenografted PDX220 Tet-On c-MYCT58A are shown in C. Error bars represent SEM. (D–F) Quantitation of IHC performed on xenografts shown in Fig. 2, taken from three regions of stained tumor sections. ns, not significant; *, P < 0.05; **, P < 0.005; ***, P < 0.0005; ****, P < 0.0001 by two-way ANOVA. (G and H) Mouse weights for each xenografted cell type (G, HPAF-II Tet-On c-MYC; H, PDX220 Tet-On c-MYC) were averaged. Error bars represent SEM. (I and J) Alisertib combined with trametinib reduces c-MYC expression in PANC-1 cells. PANC-1 lysates were blotted for c-MYC and ACTB after treatment with trametinib and/or alisertib for 48 h at the indicated concentrations. Representative blots from two (for I) and five (for J) independent experiments are shown. (K) Mouse weights of xenografted PANC-1 were averaged. Error bars represent SEM. Source data are available for this figure: SourceData FS1.

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