Fig. 3: Dual PARP and HDAC inhibitors induce DNA damage, inhibit the expression of key proteins encoding HRR genes, inhibit cell proliferation, and induce apoptosis in vitro. | Cell Death & Disease

Fig. 3: Dual PARP and HDAC inhibitors induce DNA damage, inhibit the expression of key proteins encoding HRR genes, inhibit cell proliferation, and induce apoptosis in vitro.

From: Novel dual inhibitors of PARP and HDAC induce intratumoral STING-mediated antitumor immunity in triple-negative breast cancer

Fig. 3

A The TNBC cell lines MDA-MB-231, MDA-MB-436, and MDA-MB-468 were treated with B102 or B302 at different concentrations for 48 h, and the cell lysates were analyzed by western blotting with the indicated antibodies. B MDA-MB-231, MDA-MB-436, and MDA-MB-468 cells were treated with B102 or B302 at different concentrations for 48 h, fixed, and then subjected to immunofluorescence analysis for γH2A.X; scale bars, 20 μm. C MDA-MB-231, MDA-MB-436, and MDA-MB-468 cells were treated with B102 at different concentrations, olaparib, chidamide, or olaparib in combination with chidamide for 24 h, and the cell lysates were analyzed by western blotting with the antibodies indicated. D MDA-MB-231, MDA-MB-436, and MDA-MB-468 cells were treated with B302 at different concentrations for 24 h, and the cell lysates were analyzed by western blotting with the indicated antibodies. E PARP/HDACi suppressed the mRNA expression of BRAC1 and RAD51. MDA-MB-231 cells were treated with B102 or B302 at different concentrations for 24 h. The relative mRNA expression levels of BRAC1 and RAD51 were determined by RT‒PCR assay. Data are presented as the mean ± standard deviation (SD), unpaired Student’s t test, n = 3; **p < 0.01; ***p < 0.001; ****p < 0.0001. F, G B102 and B302 inhibited the clonogenicity of TNBC cells in a dose-dependent manner. Representative colony plates of three independent experiments are shown. Magnification: ×50. H, I MDA-MB-436 cells were treated with B102 H or B302 I at the indicated concentrations for 48 h, and cells were examined with an Annexin V-FITC/PI apoptosis detection kit to detect cell apoptosis with flow cytometry. Representative results of three independent experiments are shown. J MDA-MB-231, MDA-MB-436, and MDA-MB-468 cells were treated with B102 or B302 at different concentrations, olaparib, chidamide, or olaparib in combination with chidamide for 24 h, and the cell lysates were analyzed by western blotting with apoptosis-related antibodies.

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