Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors.

The microvessel density (CD31 staining) showed a decreasing trend, and hypoxia (CA9 staining) was elevated in IGFBP‐1‐high HCC (HepG2) xenografts treated with lenvatinib (Figure 2D ‐ E ). 3.4 Therapeutic effects of lenvatinib in HCC xenograft mouse models Next, we subcutaneously implanted HuH7, a human HCC cell line with low IGFBP‐1 expression (hereafter, IGFBP‐1‐low human HCC; Figure 2A ), in nude mice (BALB/c nu/nu), and Hep‐55.1C, a mouse HCC cell line with low IGFBP‐1 expression (hereafter, IGFBP‐1‐low mouse HCC; Supplementary Figure S2A ) in immunocompetent C57BL/6 mice.

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