Fig. 6

MDM2 inhibition synergises with palbociclib to reduce proliferation via cell cycle arrest. a Growth inhibition relative to vehicle of escalating doses of NVP-CGM097 (red) and palbociclib (yellow) alone and in combination (orange) b log₂ (combination index) calculated from results in a. Values below 0 (equivalent to combination index < 1) indicate synergy. Dose points: NVP-CGM097 × 100 nM; palbociclib × 50 nM. c Venn diagram showing the overlap (green) between differentially expressed genes (adjusted p value < 0.05 and 2-fold change) induced in MCF-7 cells by treatment for 48 h with combination therapies, 1 μM NVP-CGM097 plus 1 nM fulvestrant (purple) and 1 μM NVP-CGM097 plus 500 nM palbociclib (orange). d Normalised log₂ expression levels of significant p53 target genes induced by treatment with NVP-CGM097 (1 μM); palbociclib (500 nM) and combination (1 μM NVP-CGM097 and 500 nM palbociclib), averaged by condition, associated with cell cycle, apoptosis and senescence