Fig. 7: Combining trametinib and fasting enhances the anti-neoplastic efficacy of DXR.

a Immunoblotting analysis of lysates of MDA-231 breast cancer cells treated with or without erlotinib (20 nM). b Immunoblotting analysis of SIRT7 protein stability in MDA-231 breast cancer cells treated with or without EGF (5 ng/ml), determined by CHX (50 µg/ml) chase assay. c Immunoblotting analysis of SIRT7 protein levels in MDA-231 cells treated with U0126 (2 µM) or LiCl (10 mM). d, e Immunoblotting (d) analysis of SIRT7 protein stability in MDA-231 cells transfected with the indicated siRNA, determined by CHX (50 µg/ml) chase assay. e Curves showing the related quantification, n = 3 independent experiments. f, g Immunoblotting (f) analysis of lysates of MDA-231 cells subjected to glucose deprivation (GD) for the indicated periods. Bar charts in (g) showed the related quantifications from three independent experiments. h Immunoblots showing AKT activation in MDA-231 cells expressing empty vector (EV) and relevant SIRT7 mutants with or without glucose deprivation (GD). i Immunoblotting analysis of lysates of MDA-231 cells cultured under glucose deprivation (GD) in the presence or absence of the MEK-ERK inhibitor (ERKi) U0126 (2 µM). j Immunoblots showing SIRT7 levels in lung cancer A549 cells and breast cancer MDA-231 cells with or without trametinib (20 nM) treatment. k–n Representative images (k) and growth curves (l–n) of tumors generated from Scram or Sirt7 KD 4T1 cells as indicated; Note: all groups of mice in (l) and (m) were simultaneously manipulated and curves of (n) were derived from (l) and (m). n = 5 mice per group in (l); n = 4 mice per group in (m); F intermittent fasting, T trametinib, D doxorubicin; arrows indicated drug application. Scale bars, 1 cm. Representative results were observed from at least three independent experiments or samples. Data represent means ± SEM (e, g, l–n). P values were calculated by two-tailed Student’s t-test (e, g) or two-way ANOVA analysis (l–n), ***P = 0.00003, n.s. no significance. Source data are provided as a Source Data file.