FIGURE 6.

Reversed microevolution of drug‐resistant DU145 cells increases their invasive potential. A, Proliferation of SCL‐derived DU145 lineages (ST) and their (LT) counterparts estimated after 48 hour‐long docetaxel (DCX) treatment. B, Calcein efflux intensity in dfSCL_DU145/LT and dfSCL_DU145_DCX20/LT in comparison to their ST counterparts (indicated by dotted lines/arrows). Scale bar = 200 μm. C, Motility of dfSCL_DU145/LT and dfSCL_DU145_DCX20/LT measured as % of ST control. D, Transmigration of dfSCL_DU145/LT and dfSCL_DU145_DCX20/LT cells through microporous membranes. Scale bar = 2 mm. E, Relative fractions of Snail1‐/E‐cadherin^high cells in dfSCL_DU145_DCX20/LT populations quantified with ImageStream. F, Morphology of DCX/fenofibrate (FF)‐treated dfSCL_DU145/LT and dfSCL_DU145_DCX20/LT cells. Scale bar = 50 μm. G, Effect of DCX and/or FF on the proliferation (upper panel) and displacement (lower panel) of LT DU145 and DU145_DCX20 lineages. All results are representative of a least three independent experiments (N ≥ 3). The statistical significance of the differences was tested with t‐Student test (A, B, D; #P ≤ .05 vs untreated control; *P ≤ .05 vs ST lineage or selected bars/points) or by one‐way ANOVA followed by post hoc Tukey's HSD (C, G; *P ≤ .05 vs wild‐type [WT] lineage or selected bars/points). Note the increased invasiveness of drug‐sensitive/Snail‐1^high cells undergone reversed microevolution under the limited DCX/FF bioavailability