Fig. 1. Sensitivity of ovarian cancer (OVCA) cell lines to CX-5461.

a CX-5461 doses that induce 50% growth inhibition (GI₅₀) at 48 hours. Error bars represent mean ± standard deviation (SD). Asterisks denote mutated TP53 status. The geometric mean GI₅₀ dose of 363 nM is indicated by the fine line. Information regarding each cell lines source, mean G1₅₀ values, SD and N values are outlined in Supplementary Table 1. The 12 CX-5461-sensitive and 11 CX-5461-resistant cell lines highlighted were utilised to identify CX-5461-sensitivity gene expression signatures in Fig. 2a. b CX-5461 GI₅₀ doses of TP53 wild type and TP53 mutant OVCA cell lines as outlined in (a). Statistical analysis was performed using a two-sided Mann–Whitney test. Error bars represent mean ± SD. c Baseline rDNA transcription rates of OVCA cell lines (listed in (d)), as determined by quantitative real-time PCR (qRT-PCR) analysis using primers specific to the external transcribed spacer 5’ETS (+413–521 bp) relative to the transcription start site (TSS). Expression levels in each cell line were normalised to Vimentin mRNA and expressed as fold change relative to TOV112D cells. Each dot represents the mean value of n = 3 biologically independent experiments per cell line (Individual data points are provided in Supplementary Data 4). Error bars represent mean ± SD. Statistical analysis was performed using a two-tailed unpaired t test. d Dose-response curves of 47S precursor rRNA levels measured by quantitative RT-PCR. OVCA cell lines were treated with vehicle or increasing drug concentrations of CX-5461 (0.001, 0.01, 0.03, 0.1, 0.3, 1 and 3 μM) for 1 h before RNA was harvested. Expression levels were normalised to Vimentin mRNA and expressed as fold change relative to vehicle-treated controls. Shown are the mean of n = 3 independent biological experiments for each cell line. (Individual data points are provided in Supplementary Data 4). e The mean inhibitory concentration values that led to 50% transcription inhibition (IC₅₀) (of n = 3 biologically independent experiments for each cell line) from D are presented (Individual data points are provided in Supplementary Data 4). Error bars represent mean ± SD. Statistical analysis was performed using a two-sided Mann–Whitney test.