Skip to main content
Fig. 6 | Genome Medicine

Fig. 6

From: Computational quantification and characterization of independently evolving cellular subpopulations within tumors is critical to inhibit anti-cancer therapy resistance

Fig. 6

Inhibition of expanded subpopulations sensitizes human TNBC cell lines and BR45 PDX to RT. A Survival assays show a ~ 30% cell survival rate 6 days post-RT, with TNBC regrowth to ~80–90% confluency 14 days post-RT. B Fold changes in the abundance of subpopulations b and f compared to untreated cells. These subpopulations either remained unchanged or expanded following cellular regrowth; fold change is relative to control of each time point. C Survival rates of BR45, MD-468, and MD-231 cells in response to Trastuzumab (T), Crizotinib (C), RT, RT+T, RT+C, and RT+T+C 6 days post-RT. Cellular drug treatment began 3 days prior to RT and was continued until the end of the experiment (d10). D Downstream to Her2 and cMet signaling was tested following different treatments. C+T combined with radiation-induced higher levels of cleaved caspase-3 compared to irradiation alone and irradiation with either C or T alone or C+T. C+T administration prior to RT induced the downregulation of pAKT, pERK, and p-S6 levels. E C+T sensitized TNBC response to RT in BR45 PDX in vivo. BR45 tissues were transplanted orthotopically into NSG mice treated with brachytherapy on days 3 and 5 with 12 Gy and 10 Gy, respectively. Drugs were administrated from d0 (3 days prior to RT) until the end of the experiment (d17), ± S.E. are shown. F In vivo fold changes in the abundance of subpopulations b and f in response to T and C, which is relative to control of each time point. For A, B, C, and F, ± S.D. are shown. For B, quantification of subpopulations was performed using at least ~30,000 cells from each condition, which were obtained from at least three flasks and from at least three independent experiments for each time point. For E, F, mice used for each condition: control n=6, RT n= 5, RT+T n=6, RT+C n= 6, RT+T+C n= 6, RT+T+C+E n= 6, and T+C n=7. On day 6 post-RT, 3 control mice, 2 RT mice, 3 RT+T mice, 3 RT+C mice, 3 RT+T+C mice, 3 RT+T+C+E mice, and 4 T+C mice were euthanized. On day 12 post-RT the experiment was completed and all remaining mice were euthanized. For A, C, E, and F statistically significant differences compared to cells treated with RT (A) and to cells treated with RT+T+C (C, E, F) were determined using a two-tailed Student’s t test (*P < 0.01; **P < 0.05; #P <0.3)

Back to article page