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. 2019 Mar 18;43:225–237. doi: 10.1016/j.ebiom.2019.03.027

Fig. 4.

Fig. 4

CDK4/6 inhibition by Palbociclib results in downregulation of MYC targets, sensitizing ovarian cancer cells to PARP inhibition by Olaparib. (a) GSEA of MYC gene signatures in Palbociclib-treated (left panels) or Ola/Palb-treated (right panels) A2780 cells compared to Vehicle-treated cells. (b) Quantitative reverse transcription PCR analysis of LDHA and ODC1 mRNA expression in A2780, EFO27, OVCAR8, SNU119, and COV362 ovarian cancer cell lines treated with drugs as indicated for 24 h. Mean ± S.D. for three independent experiments are shown. A2780, EFO27 and OVCAR8: Olaparib, 2 μM; Palbociclib, 1 μM. SNU119 and COV362: Olaparib, 8 μM; Palbociclib, 4 μM. (c) Normalized abundance of MYC protein in ovarian cancer cell lines that were grouped according to their treatment response to Olaparib and Palbociclib in combination (see Supplementary Fig. 6 for western blot analysis of MYC protein levels and Fig. 1 for treatment response data). (d) The synergistic effect of concomitant PARP and CDK4/6 inhibition in A2780, EFO27, OVCAR8, SNU119, and COV362 ovarian cancer cells was measured by cell viability assay after 72 h treatment. Western blot analysis of MYC protein levels in ovarian cancer cells with or without MYC-knockdown was shown. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's t-test).