Lenvatinib Suppresses Colorectal Cancer Cell Growth, Migration, and Invasion via Dual-pathway Apoptosis and
Ching-Hsuan Wu1,2, Fei-Ting Hsu3, Chun-Hsien Chen3
1Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.
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.
Insights
Lenvatinib effectively inhibits colorectal cancer (CRC) cell growth, migration, and invasion. It induces apoptosis through dual pathways and inactivates the ERK/STAT3/NF-κB signaling axis, showing therapeutic potential for CRC.
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.
Related Concept Videos
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Inhibition of Cdk Activity
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
The Intrinsic Apoptotic Pathway
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...


