combination therapy  (MedChemExpress)

Journal: Cell reports

Article Title: DNA damage response deficiency enhances neuroblastoma progression and sensitivity to combination PARP and ATR inhibition.

doi: 10.1016/j.celrep.2025.115537

Figure Lengend Snippet: Figure 6. The ATR inhibitor ceralasertib enhances olaparib-mediated inhibition of DDR-deficient NB cells (A) Cell-viability analysis in human NB cell lines following siRNA-mediated gene knockdown of DDR genes and treatment with olaparib (0.05–800 mM) + cera- lasertib (500 nM). Error bars represent mean ± standard deviation. p values represent comparisons of non-linear fits between siDDR and siControl (siCTRL) cells treated with olaparib + ceralasertib. Comparisons of best-fit values for all treatment groups are shown in Table S8. (B) Western blot analysis of phosphorylated CHK1 (p-CHK1, Ser345), phosphorylated H2A.X (Ser345, y-H2AX), and cleaved PARP in cells following control (siCTRL), PALB2 (siPALB2), and BRCA2 (siBRCA2) knockdown. Vinculin is used as loading control. Relative protein levels are quantified below each lane and normalized to vinculin followed by vehicle control drug-treated cells within each siRNA treatment. (C) casper;prkdc/ zebrafish engrafted with EGFP;MYCN;tp53/;brca2+/ NB following DMSO vehicle control and olaparib (50 mg/kg, 4 consecutive days/ week) + ceralasertib (40 mg/kg, 4 consecutive days/week) treatments. (legend continued on next page)

Article Snippet: For olaparib and ceralasertib combination treatments, engrafted fish were orally gavaged for 4 consecutive days each week for up to four weeks (1 dose per day, 4 days on, 3 days off), with DMSO vehicle control, olaparib (50 mg/kg), ceralasertib (40 mg/kg ceralasertib, Selleckchem) or both drugs (50 mg/kg olaparib +40 mg/kg ceralasertib).

Techniques: Inhibition, Knockdown, Standard Deviation, Western Blot, Control