Inhibition of CDK6 kinase activity sensitizes EOC cells to platinum in vitro Inhibition of CDK6 kinase activity sensitizes EOC cells to platinum in vitro.

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Inhibition of CDK6 kinase activity sensitizes EOC cells to platinum in vitro Inhibition of CDK6 kinase activity sensitizes EOC cells to platinum in vitro ACell viability of CBDCA‐treated OVCAR8 cells transfected with CDK6 WT, constitutive active (R31C), dominant‐negative (D163N) mutants, or empty vector (E.V.) and treated with 60 μg/ml of CBDCA for 16 h. CDK6 expression is reported in the Western blot. Data represent the mean ± SD of two independent experiments performed in triplicate (two‐sided, unpaired t‐test).BCalculation of CDDP IC50 of MDAH cells treated or not with 8 μM PD0332991 (PD) using different schedules, as indicated. Expression and phosphorylation of RB1 were used as control of PD activity. Data represent the mean ± SD of three biological replicates.CCombination index (CI) resulting from the dose–response analysis of CDDP and PD treatments, alone or in combination. Data, analyzed with Calcusyn software, were used to measure if the two drugs have a synergistic (CI < 1), additive (CI = 1) or antagonistic (CI > 1) effect.D, EColony assay (D) and quantification (E), using MDAH platinum‐resistant clones plated with parental cells at different ratios and treated as indicated (PD 8 μM and CDDP 1.5 μg/ml). Data represent the mean ± SD of two independent experiments performed in triplicate (two‐sided, unpaired t‐test).FCDDP IC50 of mixed population of parental/platinum‐resistant MDAH cells treated with increasing concentration of CDDP alone or CDDP + PD (8 μM) (n = 3 biological replicates).GGraph representing the CDDP IC50 (black line) and the normalized survival of cells treated with CDDP + PD combination (blue line) in cells plated and treated as described in (F).HCell cycle distribution evaluated by flow cytometry of MDAH cells treated as in (D).Data information: In each panel, significant differences are evidenced by asterisks (*P < 0.05, **P < 0.01, ***P < 0.001) and the exact P‐values of (A and E) are reported in Appendix Table S4.Source data are available online for this figure. Alessandra Dall'Acqua et al. EMBO Mol Med. 2017;emmm.201607012 © as stated in the article, figure or figure legend