Background: Anlotinib is a multi-target tyrosine kinase inhibitor that has been reported to have activity
against colorectal cancer. However, the mechanisms of how anlotinib mediates drug-resistance of colorectal
cancer have not been fully described. Particularly the potential mechanisms regarding the inhibition of proliferation
and induction of apoptosis remain unknown.
Objective: In this study, we intended to study the effect and related-mechanism of the proliferation, migration,
invasion and induced apoptosis of anlotinib overcoming multidrug resistant colorectal cancer cells through in
Methods: Cell viability was determined by MTT assays and the resistant index was calculated. Colony formation
and PI/RNase Staining were used for testing the proliferation of resistant cells. DAPI staining and Annexin
V-FITC/PI staining were used to detect cell apoptosis. Migration and invasion were examined by transwell. Protein
expression and activation of PI3K/AKT pathway were detected by western blot. LY294002 was used to verify
whether anlotinib overcomes the drug-resistance of CRC cells by inactivating the PI3K/AKT pathway.
Results: The results showed that the HCT-8/5-FU cells were resistant to multiple chemotherapy drugs (5-FU,
ADM and DDP). Anlotinib significantly inhibited cell viability, proliferation, migration, invasion and induced
cell apoptosis. Moreover, anlotinib down-regulated the expression of survivin, cyclin D1, CDK4, caspase-3,
Bcl-2, MMP-2, MMP-9, vimentin and N-cadherin, but up-regulated cleaved-caspase-3, Bax and E-cadherin and
blocked the activity of the PI3K/AKT in HCT-8/5-FU cells. We found anlotinib and LY294002 overcame the
drug resistance of HCT-8/5-FU cells by reducing the expression of PI3K/p-AKT.
Conclusion: Anlotinib inhibited the proliferation, migration, invasion and induced apoptosis of HCT-8/5-FU
cells, and the mechanisms may be that anlotinib conquered multidrug resistance of colorectal cancer cells via inactivating
of PI3K/AKT pathway.