Combination of triapine, olaparib, and cediranib suppresses progression of BRCA-wild type and PARP inhibitor-resistant epithelial ovarian cancer
Fig 6
The effects of cediranib on AKT signaling and the sensitivity of BRCA2-wild type and mutated EOC cells to olaparib and triapine in vitro.
PEO1 and PEO4 cells were treated with 1.25 μM cediranib, 0.75 μM triapine, or both drugs for 1 hr and then treated with various concentrations of olaparib for 72 hr. (A) MTS cytotoxicity assay was performed to determine percent survival relative to vehicle-treated controls. Data are means ± SD. (B) EOB was calculated to determine the effects of the combinations of cediranib, triapine, and olaparib on cell survival at all data points. EOB < 0 indicates antagonism. EOB = 0 indicates additivity. EOB > 0 indicates synergism. (C) PEO1 and PEO4 cells were treated with cediranib at 1.25, 2.5, and 5 μM for 24 hr. Western blot analysis was performed to determine the protein levels of phospho-AKT (Ser473), AKT, mTOR, phospho-S6 (Ser235/236), and S6. (D) PEO1 and PEO4 cells were serum-starved and then treated with 50 μM olaparib in the absence and presence of 5 μM cediranib for indicated time periods. Western blot analysis was performed to determine the protein levels of phospho-AKT (Ser473), phospho-FoxO1 (Ser248), and HSC70.