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. 2021 Apr 8;40:122. doi: 10.1186/s13046-021-01930-w

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — The combined use of olaparib and palbociclib inhibits MYC expression through the Wnt pathway. a GSEA results in olaparib-treated PARPi-sensitive MDA-MB-436 cells (AO) compared to vehicle-treated cells (AC). b GSEA results in combination-treated olaparib-resistant HCC1937 cells (BOP) compared to olaparib-treated cells (BO). c GSEA of MYC gene signatures in MDA-MB-436 (left panels) and HCC1937 (right panels) cells with different treatments. d (Left) The overlap of hallmark gene sets in GSEA, which were downregulated in combination-treated cells (BOP) but upregulated in olaparib-treated resistant HCC1937 cells (BO). (Right) The overlap of hallmark gene sets in GSEA that were downregulated in both BO and BOP. e Quantitative reverse transcription PCR analysis of CTNNB1, TCF1, Axin2 and MYC in MDA-MB-436, HCC1937 and SUM149 BRCA^mut/TNBC cell lines treated with drugs as indicated for 24 h. Mean ± S.D. for three independent experiments. f WB analysis showed the total levels of β-catenin, TCF1, Axin2, c-myc and Rad51 in three BRCA^mut/TNBC cell lines treated with drugs as indicated for 24 h. g WB analysis showed the nucleoplasmic distribution of β-catenin and the change in the Wnt pathway (c-myc, c-Jun and Rad51) in HCC1937 upon treatment with drugs as indicated for 12 h. h WB analysis showed the change in the Wnt pathway (c-myc, c-Jun and Rad51) in MDA-MB-436 upon treatment with drugs as indicated for 12 h. i Immunofluorescence analysis of the nucleoplasmic distribution of β-catenin in olaparib-resistant HCC1937 and SUM149 cells treated with drugs as indicated for 12 h. Scale bar, 7.5 μm. j Changes in nuclear β-catenin and c-myc protein levels in HCC1937 over time under the indicated treatment. k Changes in nuclear β-catenin and c-myc protein levels in SUM149 over time under the indicated treatment. l Changes in the nucleoplasmic distribution of β-catenin and c-myc in HCC1937 under different drug concentrations for 24 h. m Changes in the nuclear distribution of β-catenin and c-myc in SUM149 under different drug concentrations for 24 h. Student’s t-test; ***p < 0.001, **p < 0.01, *p < 0.05; ns, not significant. The data are presented as the means ± SEMs. Con: Control; Ola: Olaparib; Palb: Palbociclib