Fig. 8: LSD1 inhibition sensitizes HR-proficient tumors to PARPi treatment in vivo.

a Schematic diagram of A2780, SKOV3 and ES2 subcutaneous tumor model and drug delivery. Mice were treated with vehicle (30 mg/mL PEG4000 plus 12 mg/mL Tween 20 in water and 5% DMSO plus 30% PEG300 in water intraperitoneally), ZY0511 (intraperitoneally 30 mg/kg), PARPi (olaparib 30 mg/kg, niraparib 10 mg/kg and rucaparib 10 mg/kg intraperitoneally), or a combination of ZY0511 and PARPi as indicated. Schematic diagram was created with BioRender.com. b–d Tumor volume of mice bearing A2780 (b), SKOV3 (c) and ES2 (d) subcutaneous xenografts and treated with vehicle or drugs showed in a. Data represent mean ± SEM (n = 6 mice per group; two-way ANOVA). e Body weight curves of mice treated with vehicle or drugs showed in a. Data represent mean ± SEM. (n = 18 mice per group from A2780, SKOV3 and ES2 subcutaneous xenografts; two-way ANOVA). f, g Tumor volume of mice bearing SKOV3 subcutaneous xenografts (f) and ES2 subcutaneous xenografts (g). Data represent mean ± SEM (n = 6 mice per group; two-way ANOVA). h Schematic diagram of PDX model and drug delivery. Created with BioRender.com. i, j Tumor volume (i) and body weight curves (j) of mice bearing PDX and treated with vehicle or drugs showed in h. Data represent mean ± SEM (n = 6 mice per group; two-way ANOVA). k–m Western blot analysis (k) and representative images (l) and quantification (m) of IHC of indicated proteins in tumor tissues from PDX subcutaneous xenografts. α-Tubulin was used as loading control. Numbers below western blot panels represent relative quantification of the respective bands normalized to loading control by densitometry. CC3, Cleaved Caspase 3. Scale bars, 100 μm (black), 40 μm (green). Data represent mean ± SEM of three random fields of view from three different mice (one-way ANOVA). ns not significant, p > 0.05; *p < 0.05; **p < 0.01; ***p < 0.001. Source data and exact p values are provided as the Source Data file.