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. Author manuscript; available in PMC: 2025 Jun 3.
Published in final edited form as: Mol Cancer Ther. 2024 Dec 3;23(12):1801–1814. doi: 10.1158/1535-7163.MCT-24-0369

Figure 3. CDK4/6 and MEK inhibition in fibrosarcoma, PDAC and lung cancer models leads to inhibition of E2F and induction of IFN-like response.

Figure 3.

A. ENRICHR analysis identifying downregulated pathways in HT1080 cells treated with CDK4/6i (Palbociclib, 2 μM) or MEKi (Pimasertib, 0.5 μM). B. GSEA from CDK4/6i (Palbociclib, 2 μM) or MEKi (Pimasertib, 0.5 μM)-treated HT1080 cells displaying enrichment of downregulated genes in cell cycle pathways, including E2F_Targets and G2M_checkpoint. C. ENRICHR analysis identifying upregulated pathways in HT1080 cells treated with CDK4/6i (Palbociclib, 2 μM) or MEKi (Pimasertib, 0.5 μM). D. GSEA from CDK4/6i (Palbociclib, 2 μM) or MEKi (Pimasertib, 0.5 μM)-treated HT1080 cells displaying enrichment of upregulated genes in IFN alpha response pathway. E. ENRICHR analysis identifying upregulated pathways in response to CDK4/6i (Palbociclib, 0.5 μM) and MEKi (Trametinib, 25 nM) treatment in three PDAC models: MIA PaCa-2, PANC-1 and PA-TU 8988T. F. ENRICHR analysis identifying upregulated pathways in response to CDK4/6i (Palbociclib, 0.5 μM) and MEKi (Trametinib, 25 nM) treatment in three lung cancer models: A549 (left), H2030 (middle) and H460 (right). G. qPCR analysis for STAT2 and IRF9 in HT1080 cells treated with DMSO, CDK4/6i (Palbociclib, 100 nM), MEKi (Trametinib, 25 nM), or CDK4/6i and MEKi in combination for 48 h. Data displayed as mean ± SD in triplicate. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 as determined by one-way ANOVA with multiple comparisons. H. ISRE-mCherry IFN reporter assay in HT1080 cells treated with DMSO, CDK4/6i (Palbociclib, 100 nM), MEKi (Trametinib, 25 nM), or CDK4/6i and MEKi in combination for 0 – 120 h. Scale bar = 400 μm.