Fig. 6: Anlotinib delays tumorigenesis in vivo.

a Tumours of xenograft mice injected with CAL-62/Vector and CAL-62/EGFR. The mice were given by gavage with anlotinib (60 mg/kg) or control medium daily. b Quantification of tumour weights after mice sacrifice. c Tumour volumes were measured every week. d, e Images and quantifications of TUNEL assay and IHC staining of Ki67, CD31, p-EGFR (phospho-Y1068), HIF1α, CXCL11 and EGF. Red arrowhead means tumour cells, and black arrow means endothelial cells. f Xenograft models were generated by injecting CAL-62. Four groups of mice were treated with control medium, anlotinib, gefitinib and a combination of two agents. g Quantification of tumour volumes and weights of the four groups. h The schematic of anlotinib blocking cancer–endothelium crosstalk in ATC. Anlotinib inhibited hypoxia-induced positive CXCL11-EGF-EGFR feedback loop by direct binding to EGFR on both cancer and vascular cells. *P < 0.05; **P < 0.01.