Fig. 4: Inclusion of radioresistant populations in spheroids reduces radiation sensitivity. | Communications Biology

Fig. 4: Inclusion of radioresistant populations in spheroids reduces radiation sensitivity.

From: Reciprocal interactions between tumour cell populations enhance growth and reduce radiation sensitivity in prostate cancer

Fig. 4

a Survival curves of time (days) taken for irradiated PC3 spheroids seeded with 100% parental (dashed black line), 9:1 parental:radioresistant (P:RR, orange line), 1:1P:RR (blue line) or 100% RR (black line) cells to reach endpoint, adjusted for the time taken by untreated spheroids to reach the same endpoint (n = 15 spheroids/group/radiation dose from 1 batch). ***Padj < 0.001, global log-rank test for all survival curves; +Padj < 0.05, ++Padj < 0.01, log-rank test comparing survival curves of parental vs. 9:1P:RR (orange crosses). b, e Survival curves of time (days) taken for irradiated PC3 (6 Gy) and DU145 (6 and 10 Gy) spheroids seeded as parental (dashed black line), 1:1P:RR (blue line), or RR (solid black line) to reach the endpoint, adjusted for the time taken by untreated spheroids to reach the same endpoint (n = 17 spheroids/group for PC3 pooled from 3 batches; n = 12 spheroids/group for 6 Gy DU145 spheroids pooled from 2 batches; n = 20 spheroids/group for 10 Gy DU145 spheroids from 1 batch). ***Padj < 0.001, global log-rank test for all survival curves; ++Padj < 0.01, +++Padj < 0.001, log-rank test comparing parental vs. 1:1P:RR (blue crosses) and parental vs. RR (black crosses) spheroids. c, f Proportions of parental (green diamonds) and RR (pink diamonds) populations measured over time using flow cytometry from spheroids seeded as 1:1 mixture and irradiated (n = 4 experiments, ***Padj < 0.001, 2-way ANOVA with Sidak correction). Lines connecting symbols indicate the median value. d, g Percent of dead cells in each population isolated from irradiated homogeneous spheroids (parental, white circles; RR, black circles) or from mixed spheroids (parental, green diamonds; RR, pink diamonds) seeded as a 1:1 mixture of parental:RR (n = 4 experiments). Bar indicates mean value. ‡FDR < 0.05, overdispersed binomial regression with Benjamini–Hochberg correction. No P value was calculated for parental populations from DU145 spheroids on day 15 due to a poor model fit.

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