Extended Data Fig. 7: Time-dependent increased sensitivity of aneuploid cancer cells to genetic and chemical SACi.
From: Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition
a, Comparison of the doubling times of HCT116 and HPT cells exposed to siRNAs against BUB1B, MAD2 or TTK. The drug effect of SACi is stronger in the near-diploid HCT116 cells at d5, but is stronger in the highly-aneuploid HPT cells at d21. b, Comparison of the doubling times of HCT116 and HPT cells exposed to the SAC inhibitors MPI-0479605 or reversine. The drug effect of SACi is stronger in the near-diploid HCT116 cells at d5, but at d21 it becomes stronger in the highly-aneuploid HPT cells. *P = 0.034, P = 0.046 and P = 0.049 for MPI-0479605 and reversine at d5 and d14, respectively; **P = 0.0015 ; one-tailed t-test; n = 2 independent cell lines. c, Representative images of cells from the drug experiment (same images as in Fig. 2g), with cell masking performed using the image analysis software ilastik61. Scale bar, 100μm. d, The relative viability of the aneuploid RPE1 clones, SS111 and SS51, following reversine exposure. The viability effect was normalized to the effect of the drug in the near-diploid RPE1 clone, SS48. The drug effect of SACi is comparable during the first week of drug exposure, but the highly-aneuploid cells become significantly more sensitive with time. *P = 0.045, **P = 0.002, P = 0.001 and P = 0.005 for the comparisons between d3 and d14, d5 and d14 and d7 and d14, respectively; two-tailed t-test. e, The relative viability of 5 near-euploid (CAL51, EN, MHHNB11, SW48 and VMCUB1) and 5 highly-aneuploid (MDAMB468, NCIH1693, PANC0813, SH10TC and A101D) cell lines to 72h and 14 days exposure to the SAC inhibitor reversine. *P = 0.012 and P = 0.037, for 3d and 14d time points, respectively; two-tailed Wilcoxon rank-sum test.
