Extended Data Fig. 1: T/P treatment induces cellular senescence across tumor conditions in vivo.
a, Representative Hematoxylin and eosin (H&E) (top) and Masson’s trichrome (bottom) staining of indicated KPC1 PDAC (PIP, PIL, PILiver) and KP1 LUAD (LIL, LIP, LILiver) derived-tumors grown in different organs from 2-3 independent experiments. Scale bars, 100μm. b, Immunohistochemical (IHC) staining of indicated KPC1 PDAC (PIP, PIL, PILiver) and KP1 LUAD (LIL, LIP, LILiver) derived-tumors treated with vehicle (V) or combined trametinib (1 mg/kg) and palbociclib (100 mg/kg) (T/P) for 2 weeks. Quantification of the percentage of SA-β-gal+ area and the number of Ki67+ and pRb+ cells per field are shown inset (n = 2-4 independent tumors per group). Scale bar, 50μm. c, Immunofluorescence staining of indicated KPC1 PDAC (PIP, PIL, PILiver) and KP1 LUAD (LIL, LIP, LILiver) derived-tumors treated as in (b). Quantification of the percentage of GFP+ (green) tumor cells expressing p21 (cyan) is shown inset (n = 2-4 independent tumors per group). Scale bar, 50μm. d, GFP+ tumor cells were FACS sorted from indicated tumors and extracted RNA subjected to RNA-seq analysis (n = 2-4 independent samples per group). Gene Set Enrichment Analysis (GSEA) of RNA-seq data using an established senescence gene set is shown. NES, normalized enrichment score. P values in d were calculated using two-sided, Kolmogorov-Smirnov test. Error bars, mean ± SEM. IHC experiments were repeated at least twice and representative images are shown.
