FIGURE 2.

CD44⁺ stem cell‐like (SCL) cells participate in the microevolution of prostate cancer drug‐resistance in vitro and in vivo. A, DU145 cells were subcutaneously injected into abdominal flank of Severe Combined ImmunoDeficiency (SCID) mice and tumors growth was estimated for 2 to 4 weeks in the presence/absence of docetaxel (injected at 20 mg/kg b.w.). At least 10 animals were taken for each variant (N > 10). Scale bar = 250 μm. B, Effect of docetaxel (DCX) on the motility and proliferation of DU145_DCX20 and DU145_DCX50 cells estimated after 6 and 48 hours of incubation, respectively. Dotted line illustrates the data for wtDU145 cells. C, The abundance of CD133⁺/CD44⁺ SCL cells in DCX (10 nM)‐treated DU145_DCX20 and DU145_DCX50 populations (calculated as % of total cell number). D, Clonogenic potential of CD44⁺ SCL cell progenies (cf. Figure 1B; dotted line = wtDU145 cells). E, Effect of 10 nM DCX on motility (left) and proliferation (right) of nSCL_and dcxSCL‐derived lineages of DU145_DCX20 and DU145_DCX50 cells. F, Cellular apoptotic response to 10 nM DCX estimated with AnnexinV/PI assay. G, Calcein efflux intensity in nSCL_and dcxSCL_DU145 populations. Scale bar = 200 μm. The statistical significance of the differences was tested with t‐Student test (A, C, D, F, G and proliferation in B, E; #P ≤ .05 vs untreated control; *P ≤ .05 vs wild‐type [WT] lineage or selected bars) or by one‐way ANOVA followed by post hoc Tukey's HSD (A and motility in B, E; #P ≤ .05 vs untreated control; *P ≤ .05 vs WT lineage (or selected bars/points). All results are representative of a least three independent experiments (N ≥ 3). Note the microevolution of prostate cancer drug resistance under DCX stress in vivo and in vitro