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. 2021 Mar 31;11(12):5759–5777. doi: 10.7150/thno.57659

Figure 8.

Figure 8

Combined treatment of FGFR4 inhibitor BLU-554 and CXCR2 inhibitor SB265610 dramatically decreased HOXB5-driven HCC metastasis. (A) The diagram of in vivo treatment in C57/BL mice. One week after injection of PLC-PRF/5-HOXB5 cells, mice in four group were treated with vehicle, BLU-554 or SB265610 or combined treatment respectively. (B-E) In vivo assays showed that combined treatment of FGFR4 and CXCR2 inhibitors can almost block HCC metastasis totally. (B) Representative Bioluminescence images, growth rate and lung metastasis rate were shown in different groups. (C) Metastatic lung nodules were shown. (D) Survival curve was shown in different mice. (E) HE staining shown lung metastatic nodules in different mice groups. (F) Flow cytometry showed the percent of MDSCs and CD8+T cells. (G) IF showed the infiltration of MDSCs and CD8+T cell in different groups. (H) A schematic diagram illustrated the importance of FGF19-HOXB5 signaling in HCC metastasis. FGF19-FGFR4 signaling upregulated HOXB5 expression through PI3K/Akt/HIF-1α pathway. HOXB5 promoted HCC metastasis through transactivating FGFR4 and CXCL1. Combined FGFR4 inhibitor BLU-554 and CXCR2 inhibitor SB265610 almost abolished HOXB5-induced HCC metastasis. * P < 0.05.