Journal: bioRxiv
Article Title: AURKA inhibition amplifies DNA replication stress to foster WEE1 kinase dependency and synergistic antitumor effects with WEE1 inhibition in cancers
doi: 10.1101/2025.05.28.656693
Figure Lengend Snippet: A and B , Dose-response curves for determining the sensitivity of various human cancer cell lines to either adavosertib ( A ) or VIC-1911 ( B ) with multiple dose range (adavosertib: 0.0625-10 μmol/L; VIC-1911: 0.0313-2.5 μmol/L). Cell viability was determined after 4-day exposure to drugs by CellTiter-Glo assay. Cell viability was normalized to control cells. Data are shown as mean ± SEM. C and D , Representative images of cooperative correlation matrix (right) and Loewe plots (left) of HNSCC CAL27 cells ( C ) and NSCLC NCI-H520 cells ( D ) in combinational treatment VIC-1911/adavosertib. E , Status of TP53 mutation, Loewe synergy scores (LSS) and maximum synergistic area scores (LMSAS) of human cancer cell lines are shown for evaluating synergy of combinational VIC-1911 and adavosertib treatment using SynergyFinder. and synergy score >10 and red area indicate synergism. F and G , Dose-response curves of NHTBE ( F ) and BJ1 ( G ) cells treated with control, adavosertib, VIC-1911 or combination from 4-day CellTiter-Glo assay. Cell viability was normalized to control cells. Shown are the means of technical triplicates from one experiment and the data as shown mean ± SEM are representative of three independent experiments with consistent results.
Article Snippet: HNSCC (FaDu, Detroit 562, CAL27, SCC25, and SCC-9), lung cancer (NCI-H520, NCI-H358, NCI-H1437, A549, NCI-H441, NCI-H23 and NCI-H1792), ovarian cancer (A2780 and SK-OV3), pancreatic cancer (MiaPaCa-2), hepatocellular carcinoma (HepG2), and normal human fibroblast BJ1 cell lines were purchased from the American Type Culture Collection (ATCC); HNSCC SCC61 cell line was purchased from Sigma-Aldrich; the UNC7 is a patient-derived cancer cell line ( kind gift of Wendell Yarbrough, University of North Carolina ) and PCI-13 isogenic cell lines of differing TP53 including WT, null, G245D, C238F or R273H genotypes were kindly provided by Jeffrey Myers (MD Anderson Cancer Center).
Techniques: Glo Assay, Control, Mutagenesis
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