Anlotinib suppresses metastasis and multidrug resistance via dual blockade of MET/ABCB1 in colorectal carcinoma cells

Anlotinib, a highly selective multi-targeted tyrosine kinase inhibitor (TKI) has therapeutic effects on non-small-cell lung cancer (NSCLC). In this study, the anti-tumor activity and molecular mechanism of anlotinib in metastatic colorectal cancer (mCRC) was explored. The anti-angiogenesis, anti-metastasis, anti-proliferative, and anti-multidrug resistance efficacy of anlotinib were analyzed by using in vitro and in vivo models of human CRC cells. The results indicated that anlotinib boosted chemo-sensitivity of CRC cells, and restrained its proliferation. Besides the suppression of the MET signaling pathway, anlotinib also inhibited invasion and migration of CRC cells. Furthermore, anlotinib prevented VEGF-induced angiogenesis, N-cadherin (CDH2)-induced cell migration, and reversed ATP-binding cassette subfamily B member 1 (ABCB1) -mediated CRC multidrug resistance in CRC. The CRC liver metastasis and subcutaneously implanted xenograft model testified that anlotinib could inhibit proliferation and liver metastasis in CRC cells. Such an observation suggested that a combination of anlotinib with anti-cancer drugs could attenuate angiogenesis, metastasis, proliferative, and multidrug resistance, which constitutes a novel treatment strategy for CRC patients with metastasis.