Anlotinib inhibits c-MET and ITGA2 in the treatment of anaplastic thyroid carcinoma.

OBJECTIVE: This study explored the therapeutic effects of anlotinib in anaplastic thyroid carcinoma (ATC) models and the underlying molecular mechanisms. METHODS: Human C643 and CAL-62 anaplastic thyroid carcinoma cell lines were cultured in vitro and treated with anlotinib. The effects of anlotinib on the proliferation, apoptosis, cell cycle progression, migration, and invasion of C643 and CAL-62 cells were observed. The tumour volumes and body weights of BALB/c-nu mice bearing subcutaneous tumours were recorded within 14 days of anlotinib treatment. HE staining and immunohistochemical staining for Ki67 and CD31 were performed on the tumour tissues from the mice. We collected anlotinib-treated and untreated C643 cell samples for subsequent transcriptome sequencing and analysis. Western blotting was conducted to measure the protein expression of c-MET, p-MET, LAMC2, COL5A1, and ITGA2 in mouse tumour tissues and C643 cell samples. RESULTS: Anlotinib inhibited the growth of C643 and CAL-62 cells in a dose-dependent manner. Anlotinib also induced apoptosis and caused cell cycle arrest at the G2/M phase in C643 and CAL-62 cells (p < 0.05). Anlotinib significantly reduced the migration and invasion of C643 and CAL-62 cells (p < 0.001). Moreover, anlotinib effectively suppressed the growth of subcutaneously transplanted tumours in mice (p < 0.05). Immunohistochemical staining for Ki67 and CD31 demonstrated that anlotinib significantly inhibited tumour cell proliferation and angiogenesis. Furthermore, anlotinib downregulated the protein expression of p-MET, LAMC2, COL5A1, and ITGA2 in mouse tumour tissues and C643 cells (p < 0.05). CONCLUSION: This study confirmed the therapeutic effect of anlotinib on ATC via in vivo and in vitro experiments. In addition, preliminary studies suggest that the mechanism of anlotinib in treating ATC may be to alter the high invasiveness of ATC cells by inhibiting c-MET signaling pathway.