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

Sep 28, 2026

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Colorectal cancer (CRC) is a major cause of cancer mortality, and the anticancer effects of the multi-kinase inhibitor lenvatinib in CRC require clarification. This in vitro study assessed human CRC cell lines HT-29 and HCT-116 treated with lenvatinib, evaluating viability, proliferation, apoptosis, migration, and invasion. Signaling mechanisms were analyzed by western blot. Lenvatinib reduced viability in a dose- and time-dependent manner, induced dual-pathway apoptosis, and inhibited ERK phosphorylation with inactivation of STAT3/NF-κB signaling, markedly suppressing motility and invasion. Results indicate therapeutic potential for CRC.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Background/Aim

Materials and Methods

Results

Conclusion

Introduction

Clinical context and treatment options

Rationale for lenvatinib in cancer

Materials and Methods

Cell culture

Experimental assays

doi: 10.21873/invivo.14189 Lenvatinib Suppresses Colorectal Cancer Cell Growth, Migration, and Invasion via Dual-pathway Apoptosis and ERK/STAT3/NF-κB Inactivation CHING-HSUAN WU1,2, FEI-TING HSU3, CHUN-HSIEN CHEN3, PEI-EN WANG3, HUAI-YI HUANG4, LING-LING HSIEH2 and CHENG-HSIEN CHEN5 1 Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.; 2 Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.; 3 Department of Life Sciences, National Central University, Taoyuan, Taiwan, R.O.C.; 4 Division of Gastroenterology and Hepatology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.; 5Surgical Intensive Care Unit, Department of Surgery, Changhua Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C. Abstract 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 (MTTassay), 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. Keywords: Colorectal cancer, lenvatinib, apoptosis, ERK/STAT3/NF-κB, proliferation. TalechnoIntenlogysive, TaichungCare Unit,,TaiDewanpart,Rm.Oen. Ct .TofelSu: +886rgery0, 42239Chang1h647ua S\#h7o1w16Ch, ew-manailM:lelhsiehmoria2l013@Hospigmtal,aCilh. comangh; Dura,. ChengTaiwan-H, sienR OCChenTel,: Dr. Ling-Ling Hsieh, Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and +886 933283767, [e-mail: picorna@gmail.com](e-mail: picorna@gmail.com) Received September 26, 2025 | Revised October 28, 2025 | Accepted November 4, 2025 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ©2026 The Author(s) . Anticancer Research is published by the International Institute of Anticancer Research. Introduction Colorectal cancer (CRC), the third most commonly diagnosed cancer and the second leading cause of cancerrelated death worldwide, is projected to double in incidence by 2035 due to genetic, lifestyle, and inflammatory risk factors (1, 2). The standard and conventional treatment modalities for colorectal cancer (CRC) primarily include surgical resection for resectable lesions. For unresectable CRC, radiotherapy, chemotherapy, immunotherapy, and targeted therapy are commonly employed. In addition, various combination treatment strategies are widely applied in clinical practice, such as targeted therapy combined with chemotherapy or immunotherapy-based regimens. Conventional therapies lack specificity and are prone to adverse effects and drug resistance, highlighting the urgent need for novel molecularly targeted strategies to broaden cancer treatment options (3-5). Lenvatinib, an orally multitarget tyrosine k

FAQs

What was the primary goal of the study on lenvatinib and CRC cells?

The study aimed to identify lenvatinib’s potential treatment mechanism and its efficacy on colorectal cancer cells in vitro.

How did lenvatinib affect CRC cell growth and proliferation?

Lenvatinib reduced cell viability in a dose- and time-dependent manner and suppressed colony formation, indicating inhibition of growth and proliferation.

Which apoptosis and signaling pathways were implicated by the study?

Apoptosis occurred through extrinsic (Fas/Fas-L and cleaved caspase-8) and intrinsic (cleaved caspase-9 and mitochondrial dysfunction) pathways. ERK phosphorylation was inhibited, with subsequent inactivation of STAT3 and NF-κB signaling.

Sep 28, 2026

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