Dose-dependent effects of TKIs on sarcoma cell line viability and CSC enrichment
. 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. SSChi 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 ALDHbright 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 ALDHbright 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.