Fig. 5: CX-5461 plus topotecan inhibits HR-proficient HGSC clonogenic survival and tumour growth. | British Journal of Cancer

Fig. 5: CX-5461 plus topotecan inhibits HR-proficient HGSC clonogenic survival and tumour growth.

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. 5

a Clonogenic survival assays for OVCAR4 cells treated with vehicle or approximate GI50 doses of CX-5461 in the absence or presence of the indicated concentrations of cisplatin or topotecan for 48 h. Drugs were washed out and cells were cultured for an additional 5 days, fixed and stained with crystal violet. Relative colony area normalised to vehicle without cisplatin is presented as mean ± SEM and statistical significance for the decrease in relative colony area was determined by one-way ANOVA (*P < 0.05; **P < 0.01; ****P < 0.0001; CX-5461 with cisplatin vs. CX-5461 with topotecan, ##P < 0.01). b Mean tumour volume of OVCAR3 flank tumours treated with vehicle, CX-5461 (30 mg/kg), topotecan (5 mg/kg) or CX-5461 (30 mg/kg) and topotecan (5 mg/kg) (n = 10 mice/group). Data are presented as mean ± SEM and statistical significance was determined on day 22 by one-way ANOVA (vehicle vs. CX-5461, topotecan or combination, CX-5461 vs. topotecan or combination, ****P < 0.0001; topotecan vs. combination, ***P < 0.001). c Kaplan–Meier survival curves of tumour-bearing mice. Statistical significance was determined by log-rank Mantel–Cox tests (vehicle vs. CX-5461, CX-5461 vs. topotecan, *P < 0.05; vehicle vs. topotecan or combination, CX-5461 vs. combination, ****P < 0.0001; topotecan vs. combination, ***P < 0.001). d Mouse body weight. Dashed line indicates day of drug dosing.

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