Fig. 7: RS-35d exerts intrinsic synthetic lethality in PARPi-resistant, BRCA2-mutated Capan-1/OP 2D and 3D cultures. | Cell Death Discovery

Fig. 7: RS-35d exerts intrinsic synthetic lethality in PARPi-resistant, BRCA2-mutated Capan-1/OP 2D and 3D cultures.

From: Investigating synthetic lethality and PARP inhibitor resistance in pancreatic cancer through enantiomer differential activity

Fig. 7

Cell viability after 72 h exposure to 10 µM olaparib (OLA), 2 µM talazoparib (TAL), 10 µM rucaparib (RUC) or 10 µM AZD2461 (AZD), alone or in combination with 40 µM RS-35d, 20 µM S-35d or 20 µM R-35d in Capan-1/OP 2D (a) and 3D (b) cultures. c Evaluation of the effect of the 72 h treatment with 40 µM RS-35d on Capan-1/OP 3D spheroid volume and cell death. Time-course representative brightfield and fluorescence images of Capan-1/OP 3D spheroids treated as previously described (scale bar, 200 μm), analysis of the corresponding 3D spheroid volume (expressed as % of the spheroid volume at t = 0 h) and cell death in 3D spheroid at 72 h (expressed as PI/Calcein-AM ratio). Results are expressed as mean ± SD (n = 6). Statistical analysis was performed with Student’s t-test (c right) or two-way ANOVA (a, b, c middle), followed by Tuckey’s multiple comparison test, with §p < 0.05, §§p < 0.01 or §§§p < 0.001 vs CTRL; ##p < 0.01 or ###p < 0.001 vs PARPi alone.

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