Lenvatinib Inhibits AKT/NF-κB Signaling and Induces Apoptosis Through Extrinsic/Intrinsic Pathways in Non-small Cell Lung Cancer

• Published in: Anticancer research Vol. 41; no. 1; pp. 123 - 130
• Main Authors: Liu, Yu-Chang, Huang, Bo-Han, Chung, Jing-Gung, Liu, Wei-Lin, Hsu, Fei-Ting, Lin, Song-Shei
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.01.2021
• Subjects: AKT protein; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung - metabolism; Cell activation; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell viability; Enzyme inhibitors; Flow Cytometry; Gene flow; Growth factors; Humans; Inactivation; Kinases; Lung cancer; Lung Neoplasms - metabolism; Metastases; NF-kappa B - metabolism; NF-κB protein; Non-small cell lung carcinoma; Phenylurea Compounds - pharmacology; Protein Kinase Inhibitors - pharmacology; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Quinolines - pharmacology; Reporter gene; Signal transduction; Signal Transduction - drug effects; Signaling; Small cell lung carcinoma; Therapeutic targets; Vascular endothelial growth factor; Western blotting; non-small cell lung cancer; NF-κB; apoptosis; AKT; Lenvatinib
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14757

Non-small cell lung cancer (NSCLC) is a serious disease and the leading cause of death globally. Overexpression of protein kinase B/nuclear factor-kappa B (NF-κB) signaling transduction of NSCLC cells was recognized as a potential therapeutic target. Lenvatinib is a multiple kinase inhibitor against vascular endothelial growth factor receptor family. However, whether lenvatinib may affect AKT/NF-κB in NSCLC remains unknown. MTT assay, NF-κB reporter gene assay, flow cytometry, tranwell migration/invasion analysis and western blotting were used to identify the alteration of cell viability, NF-κB activation, apoptosis effect, migration/invasion potential and AKT/NF-κB related protein expression, respectively, in CL-1-5-F4 cells after lenvatinib treatment. The cell viability and NF-κB activity were suppressed by lenvatinib. Extrinsic and intrinsic apoptosis were activated by lenvatinib. Additionally, the metastatic potential of CL-1-5-F4 cells was also suppressed by lenvatinib. Altogether, lenvatinib induced extrinsic/intrinsic apoptosis and suppressed migration/invasion ability of NSCLC cells that was associated with AKT/NF-κB signaling inactivation.