FIGURE 4 from PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies
Year: 2023
Type: other
Abstract: PRMT5 inhibition induces DNA repair deficiency, and synergizes with PARP inhibition and chemotherapy in vitro and in vivo. A, Cell proliferation of HR-proficient ovarian cancer cell lines was assessed by cell-titer glo assays following 10 days treatment with C220 (n = 3). B, Immunofluorescent detection of γH2AX foci in ES-2 cells treated with C220, olaparib, or in combination for 4 days. Images are taken at 20x and are representative of two biological replicates. C, Quantitation of average γH2AX foci/nuclei (>250 nuclei/condition, n = 2). D–F, Cell proliferation assays in ovarian cancer cell lines following treatment with olaparib, cisplatin, 5-FU, or C220 alone or in combination for 10 days. Data represent percent cell proliferation relative to DMSO controls and the average response of three biological replicates is shown. G, ZIP scores were calculated from average percent cell proliferation data from drug combination using SynergyFinder. H,In vivo mouse ovarian cancer PDX (CTG-0703, BRCA1 deletion) treated with PRT543, olaparib, or in combination (n = 10 mice/group). I,In vivo mouse breast cancer PDX (CTG-1242, HR proficient) treated with PRT543, olaparib, or in combination (n = 10 mice/group). Data are represented as mean ± SEM. H and I, asterisks indicate statistical significance noted by connecting bars (*, P <0.05; **, P <0.01) using a Mann–Whitney test.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4388424081