Fig. 2

Olaparib extensively suppressed the DNA damage repair signaling and key pluripotent transcriptional factors potentially through chromatin remodeling protein CHD1L. a Hierarchical clustering analysis of residual tumors after treatment with Olaparib, Sorafenib, and vehicle control. b Gene ontology analysis of differentially expressed genes in different subgroups of residual tumors after drug treatment. c The representative DNA damage repair gene expression profiling in PLC-8024 cells treated with Olaparib, Sorafenib, combination of both and vehicle control was examined by qPCR, Mann-Whitney test. d Representative DNA damage repair gene expression profiling in wildtype PLC-8024 cells and CHD1L knock out PLC-8024 cells (8024-sgCHD1L) treated with Olaparib, Mann-Whitney test. e The binding of PARP1, CHD1L to the promoter regions of the representative DNA damage repair gene, as well as the active transcription histone marker H3K4me3 were examined by ChIP-qPCR both in wildtype PLC-8024 cells and 8024-sgCHD1L cells. Mann-Whitney test. f HCC cell lines PLC-8024 and HepG2 were treated with increasing doses of Olaparib, and the relative expression of key pluripotency transcriptional factors SOX2, OCT4, c-MYC were examined by qPCR. g PLC-8024 cells were treated with Olaparib at different concentrations (5 μM, 50 μM) and the relative expression of SOX2, OCT4, c-MYC were detected by western blot. The activity of PARP1 after Olaparib treatment was also examined by western blot. h SOX2, OCT4, c-MYC were detected by western blot at different time points after Olaparib treatment. i Genomic DNA extracted from PLC-8024 cells treated with or without Olaparib was further treated with 8 U MNase. The relative nucleosome occupancy at specific regions (− 300 bp to + 200 bp) nearby the transcription start sites (TSSs) of SOX2, OCT4, and c-MYC was detected by qPCR, independent t test. j Genomic DNA was treated with the indicated amount of MNase (0-40 U). The fraction of uncut DNA fragments at the TSSs of SOX2, OCT4, c-MYC and (k) DNA damage repair genes was determined by qPCR, independent t test. The half inhibitory MNase Unit was calculated and presented in the form of heatmap. (l) Model of Olaparib in potentiating Sorafenib in HCC treatment. *, P < 0.05, **, P < 0.01, ***, P < 0.001, ****, P < 0.0001