Combination of triapine, olaparib, and cediranib suppresses progression of BRCA-wild type and PARP inhibitor-resistant epithelial ovarian cancer
Fig 4
The effects of olaparib, triapine, and cediranib combinations on peritoneal progression of PEO4ip xenografts and the survival time of mice.
SCID-Beige mice were inoculated i.p. with PEO4ip cells. After 3 days, mice were randomly assigned to 8 groups (n = 5) and treated i.p. with vehicle, single, double, and triple combinations consisting of cediranib (0.75 mg/kg), olaparib (50 mg/kg), and triapine (10 mg/kg) daily for two 3-week periods with a 2-week treatment-free period in between (day 3 to 24 and day 38 to 59). The abdominal circumference was measured and the body condition was monitored every 2–3 days. (A, B) Ascitic fluid smears on ThinPrep slides showed three-dimensional malignant cell clusters with papillary arrangement. (C) High-power microscopic view showed cells with cytological features consistent with ovarian high-grade serous carcinoma. (D) Peritoneal progression of PEO4ip xenografts leading to ascitic development was determined and expressed as a percent increase in abdominal circumference at day 62. Data are means ± SE. p values were determined by the one-way ANOVA with the Dunnett’s multiple comparison test compared with the control. Tumor-free control is the group of mice (n = 2) without implantation of PEO4ip cells. (E, F) The Kaplan-Meier survival curve was determined using a 50% increase in abdominal circumference and BCS2 as the endpoint. p values were determined by the Mantel-Cox test compared with the control. Olap, olaparib; Ced, cediranib; Triap, triapine.