Lenvatinib Suppresses Colorectal Cancer Cell Growth, Migration, and Invasion via Dual-pathway Apoptosis and ERK/STAT3/NF-κB Inactivation

Background/Aim: Colorectal cancer (CRC) remains a major cause of cancer mortality. Lenvatinib, a multi-kinase inhibitor, has emerging anticancer potential, but its effects in CRC are not fully defined. The aim of this study was to identify potential treatment mechanism and efficacy of Lenvatinib on CRC in vitro. Materials and Materials: Human CRC cell lines HT-29 and HCT-116 were treated with lenvatinib. Cell viability (MTT assay), proliferation (colony formation), apoptosis (flow cytometry), migration, and invasion (Transwell assay) were assessed. Key signaling pathways were analyzed by western blot. Results: Lenvatinib reduced viability in a dose- and time-dependent manner (IC50≈30 μM at 24 h) and suppressed colony formation. Apoptosis occurred via extrinsic (Fas/Fas-L upregulation, cleaved caspase-8) and intrinsic (cleaved caspase-9, mitochondrial membrane potential loss) pathways. ERK phosphorylation and downstream STAT3/NF-κB activation were inhibited. Migration and invasion were markedly reduced. Conclusion: Lenvatinib inhibits CRC cell growth, migration, and invasion by inducing dual-pathway apoptosis and inactivating the ERK/STAT3/NF-κB signaling axis, supporting its potential as a therapeutic strategy for colorectal cancer.