Fig. 5

CBL0137 exerts a synergistic anti-cancer activity with PARPi in HGSCs. A OVCAR-8 and OVCAR-4 cells were seeded (3000 cells/well) in the 6-wells plate and treated with or without 0.1 μM CBL0137 for 24 h prior to the treatment with Olaparib (0-5 μM) for subsequent 14 days. B Combination index (CI) was calculated using CompuSyn software. Synergistic effects, additive effects, and antagonistic effects are defined by CI values of < 1, =1, and > 1, respectively. C DF149 cells were seeded (50,000 cells/well) in the 6-wells plate and treated with or without 0.5 μM CBL0137 for 24 h prior to the treatment with Olaparib (0 or 2.5 μM) for subsequent 14 days. The cells were then stained by crystal violet. Quantification of the colonies of combination treatments with Olaparib in all cell lines were measured by reading crystal violet absorbance after destaining. D NRG mice bearing HGSC patient-derived luciferase-tagged DF149 tumor cells were treated with vehicle, CBL0137, Olaparib, or combination for 2 weeks (n = 5 mice in control and olaparib groups, n = 4 mice in CBL0137 and combination groups as one mouse from each group was euthanized due to CBL0137-induced tail necrosis before the endpoint). For combination group, mice were treated with CBL0137 24 h prior to Olaparib treatment. Tumor growth was monitored by bioluminescence imaging and survival of tumor-bearing mice was monitored. Representative images and quantification analysis of tumor burden on day 0 and day 21 is shown. E The Kaplan-Meier survival analysis of mice from each treatment group was performed. Log-rank test was applied for statistical significance analysis (P = 0.0021). F The Kaplan-Meier survival analysis on mice bearing LP28 HGSC PDX following treatment with CBL0137 or carboplatin alone and in combination. Log-rank test was applied for statistical significance analysis (P = 0.0001)