Lenvatinib Suppresses Colorectal Cancer Cell Growth, Migration, and Invasion via Dual-pathway Apoptosis and...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Colorectal cancer (CRC) is a leading cause of cancer mortality.
• Lenvatinib, a multi-kinase inhibitor, shows promise for cancer treatment.
• The precise mechanisms of lenvatinib in CRC require further elucidation.

Purpose of the Study:

• To investigate the therapeutic efficacy of lenvatinib on colorectal cancer (CRC) cell lines.
• To identify the underlying molecular mechanisms of lenvatinib's action in CRC.
• To evaluate lenvatinib's impact on CRC cell viability, proliferation, apoptosis, migration, and invasion.

Main Methods:

• Human CRC cell lines (HT-29, HCT-116) were treated with lenvatinib.
• Cell viability was assessed using MTT assays.
• Proliferation, apoptosis, migration, and invasion were evaluated by colony formation, flow cytometry, and Transwell assays, respectively.
• Key signaling pathways were analyzed via western blot.

Main Results:

• Lenvatinib significantly reduced CRC cell viability and colony formation in a dose- and time-dependent manner.
• Apoptosis was induced through both extrinsic (Fas/Fas-L, caspase-8) and intrinsic (caspase-9, mitochondrial potential) pathways.
• Lenvatinib inhibited ERK phosphorylation and downstream STAT3/NF-κB activation, reducing cell migration and invasion.

Conclusions:

• Lenvatinib demonstrates potent inhibition of colorectal cancer cell growth, migration, and invasion.
• The drug induces apoptosis via a dual-pathway mechanism.
• Inactivation of the ERK/STAT3/NF-κB signaling axis is a key mechanism of lenvatinib's anti-cancer effect in CRC.
• Lenvatinib presents a potential therapeutic strategy for colorectal cancer.