Fig. 2: The TOP1 inhibitor topotecan synergises with CX-5461 in multiple HR-proficient HGSC cell lines. | British Journal of Cancer

Fig. 2: The TOP1 inhibitor topotecan synergises with CX-5461 in multiple HR-proficient HGSC cell lines.

From: The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer

Fig. 2

a 2D mapped surface Combenefit BLISS plots show synergy scores for OVCAR4, OVCAR3 and CAOV3 cells treated in drug checkerboard assays with the indicated concentrations of CX-5461 and topotecan for 9 days. The range of concentrations for each drug was determined based on the GI25–GI50 dose at 5 days (Table S7). b Cell cycle analysis of OVCAR4, OVCAR3 and CAOV3 cells treated with vehicle, CX-5461 (80 nM, OVCAR4; 40 nM, OVCAR3; 360 nM, CAOV3; GI50 for proliferation at 48 h), topotecan (6 nM, OVCAR4; 2 nM, OVCAR3; 15 nM, CAOV3; GI50 for proliferation at 48 h) or CX-5461 and topotecan. Quantification of the percentage of G1, early S, late S and G2/M phase cells is presented as mean ± SEM and statistical significance was determined by Kruskal–Wallis one-way ANOVA (*P < 0.05; **P < 0.01; ****P < 0.001; ****P < 0.0001). c Representative Western blot analysis of DDR signalling in OVCAR4, OVCAR3 and CAOV3 cells treated with vehicle, 1 μM CX-5461, 20 nM topotecan, CX-5461 and topotecan or 1 μM doxorubicin for 3 or 24 h (n = 3 experiments). The concentration for each drug was determined based on the TGI dose at 2 days. Actin was probed as a loading control.

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