Fig. 1: Sensitive and resistant cell growth, treatment effects, and ribociclib-induced facilitation.

a CAMA-1 spheroids of 100% monoculture sensitive (venus, green) or resistant cells (cerulean, blue) cultured in untreated control, 200 nM ribociclib, and 400 nM ribociclib-treated medium for 18 days. Images taken on Day 18. b Growth curves of CAMA-1 untreated and ribociclib-treated (400 nM) sensitive and resistant cell populations. c CAMA-1 spheroids of different cell compositions (100% sensitive—green, 50% sensitive–50% resistant, 100% resistant—blue) cultured in untreated, 200 nM ribociclib, and 400 nM ribociclib-treated medium for 18 days. Images taken on Day 18. d Box plot of CAMA-1 log fold change of untreated and ribociclib-treated (400 nM) sensitive or resistant cells from day 0 to day 14 in monoculture and coculture. Box plots with centerline = median, box = 25th–75th percentile, and whiskers = 5th–95th percentile, outliers = open circles, n = 3 for each case, tests are two-tailed linear models. In monoculture, sensitive cells have a significantly higher reduction in growth than resistant cells (p = 6.44e-6 estimated interaction term between cell type and treatment, coefficient = −0.00565, SE = 0.000544, t = 10.376). Sensitive cells have a significantly lower growth reduction in coculture than in monoculture (p = 1.20e-7 estimated interaction term between composition and treatment, coefficient = −0.00422, SE = 0.000242, t = 17.423). Resistant cells show a more weakly significant growth reduction in coculture than in monoculture (p = 0.026 estimated interaction term between composition and treatment, coefficient = −0.00154, SE = 0.000565, t = 2.722). e Box plots of the competitive effect of sensitive (S) cells on resistant (R) cells and vice versa for CAMA-1 cells (p = 3.14e-4 with a two-tailed t-test, t = −8.0377, the difference in means is 1.391 with 95% confidence interval (−1.824973,−0.957466), n = 5). Box plots with centerline = median, box = 25th–75th percentile, and whiskers = 5th–95th percentile, outliers = open circles, n = 3 for each case, tests are two-tailed. f Facilitation measured as log observed growth relative to expected growth averaged over all replicates for CAMA-1 cells (p = 0.00061 for interaction of cell type with day using a linear model of the log of observed over expected cell number as a function of time, coefficient = 0.2125, SE = 0.0566, t = 3.76). Source data provided in Source Data files fig1ddat.csv and fig1edat.csv.