Figure 1

Dose-dependent effects of TKIs on sarcoma cell line viability and CSC enrichment in vitro . A673 (Ewing’s sarcoma), SK-LMS (leiomyosarcoma), and SW982 (synovial sarcoma) cells were exposed to increasing doses of sorafenib, pazopanib, and regorafenib for 18 – 24 hours. SSC^hi cells were then analyzed by flow cytometry using 7AAD as a cell viability stain, and ALDH expression was assessed using ALDEFLUOR™ reagents. Total cell counts and cell percentages relative to parent populations were determined. A – C. Cell viability was significantly inhibited in all cell lines at increasing doses of sorafenib, while no significant differences with pazopanib were observed. D – F. Significant enrichment of ALDH^bright sarcoma populations was observed in all cell lines following exposure to increasing doses of sorafenib, while negligible differences were observed with pazopanib. G. Sorafenib and regorafenib exert anti-proliferative effects on SW982 cells, although sorafenib is more potent than regorafenib. H. Sorafenib and regorafenib show similar enrichment for ALDH^bright CSCs. In each panel, a representative experiment of 3 replicates is shown. * P < 0.05, ** P < 0.01, and *** P < 0.001 via one-way ANOVA with Tukey’s post-test compared to dose level 0.