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• W4361825412 abstract "<p>PARP1 inhibition restores phosphorylated STAT1 from poly(ADP-ribosyl)ation and triggers synthetic lethality in LKB1-deficient cells. (a) A549 lung cancer cells were transfected with lentivirus expressing the indicated genes (LV-Ctrl, LV-LKB1-WT, and LV-LKB1-Mut) followed by treatment with olaparib (5μM) for 24 hours. The expression of pSTAT1 and PARP1 was analyzed by western blotting. (b-d) LLC1-shLkb1 and LLC1-shCtrl cells were pre-treated with olaparib (5μmol/L) for 6 hours and then stimulated with IFNγ for another 24 hours. Total pSTAT1 and STAT1 were quantified using western blot (b) and cell-surface PD-L1 was measured by flow cytometry (c). Q-PCR analysis was used to detect the expression of CXCL9 and PD-L1 (d). (e, f) The three groups of A549 cells were treated with IFNγ or IFNγ/olaparib and then refreshed the culture medium. The ratio of CD8+ T (effector cells) to A549 cells (target cell) ratio was 5:1. After 6 hours of incubation, QT-PCR analysis was used to detect the expression of indicated molecules of CD8+ T cells. (g) CD8+ T cells were treated with PBS or olaparib (5μmol/L) for 24 hours, and then the cells were collected for quantification of GZMB, PRF1, TNF, and IFNγ. CD8a was selected as the reference gene. (h) LLC-LV-Ctrl cells were treated with IFNγ/anti-PD-1 antibodies (20 μg/mL) in the absence or presence of olaparib (5 µM) or BMDCs (Tumor cells: DCs= 1:1) for 24 hours. Flow cytometry assay was used for apoptosis analysis of tumor cells. The right graph showed the quantification of tumor cell apoptosis. The data are presented as the mean ± SD of triplicate experiments. Statistical significance was determined by Student's t-test; ns, not significant; ****, P < 0.0001; ***, P < 0.001; **, P < 0.01; *, P < 0.05.</p>" @default.
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• W4361825412 date "2023-03-31" @default.
• W4361825412 modified "2023-10-13" @default.
• W4361825412 title "Figure S4 from PARP Inhibition Induces Synthetic Lethality and Adaptive Immunity in LKB1-Mutant Lung Cancer" @default.
• W4361825412 doi "https://doi.org/10.1158/0008-5472.22433577.v1" @default.
• W4361825412 hasPublicationYear "2023" @default.
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