Fig. 5

Copanlisib and alpelisib suppress neuroblastoma xenografts growth in nude mice. a–c KELLY cells were inoculated to nude mice subcutaneously to establish tumor xenograft. Tumor-bearing mice were treated with either vehicle (PBS) or copanlisib dihydrochloride every 2 days (intraperitoneal injection, 6 mg/kg, 9 days). The tumor volume (b) and body weight (c) of each mouse were recorded. Isolated tumors were pictured (a) on the last day. d–f KELLY cells were subcutaneously injected into nude mice. Tumor-bearing mice were then treated with vehicle (5% DMSO, 40% PEG300, 5% Tween-80, 50% PBS) or alpelisib (daily, oral gavage, 30 mg/kg, 10 days). g–j Tumor xenografts were processed to paraffin embedding and sectioning. pH3 was detected by immunohistochemistry (n = 4). Low magnification (g1-2, i1-2, scale bar = 500 µm) and higher magnification (g1’-2’, i1’-2’, scale bar = 100 µm) views were shown. pH3 positive cells were counted with Fiji (h, j). k–n Total pH3 levels in each tumor sample were detected by western blot. Quantification of the results was performed with Image J (l, n). Statistical significance was analyzed with Wilcoxon Signed Rank Test. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant