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. 2023 Oct 20;9:85. doi: 10.1038/s41523-023-00588-1

Fig. 6. The combination of Olaparib and Sorefenib results in DNA damage, cell cycle arrest, and apoptosis.

Fig. 6

A The level of DNA double-strand breaks was indicated by γ-H2AX foci by immunofluorescence. Bar length: 10 μm. B The protein expression level of cleaved caspase and γ-H2AX. C Cell cycle rate under different drugs obtained through flow cytometry. D The cell apoptosis rate was measured by flow cytometry. The gating strategy is provided in Supplementary Fig. 2. C, D Data are shown as the mean ± SD. One-way ANOVA analysis is used. E The mechanism of the synergic effect between Olaparib and Sorafenib. Sorafenib indirectly inhibits BRCA1 through TRIM21-mediated ubiquitination, thus inactivating the homologous recombination (HR) repair pathway. Meanwhile, Olaparib inhibits PARP, which is mainly responsible for SSBs repair. The combination of these two drugs is synergistically lethal to TNBC cells. The significant level was identified by *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001.