Lenvatinib Induces AKT/NF-κB Inactivation, Apoptosis Signal Transduction and Growth Inhibition of Non-small Cell Lung Cancer In Vivo

Abstract

Background/Aim: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Lenvatinib is a multi-kinase inhibitor that has the potential to suppress tumor progression. Our previous study suggested that lenvatinib induces cytotoxicity and apoptosis in CL-1-5-F4 cells in vitro. However, whether lenvatinib suppresses NSCLC progression in vivo remains unclear. Materials and Methods: Tumor growth inhibition and normal tissue toxicity evaluation following lenvatinib treatment were performed on CL-1-5-F4-bearing mice. Results: Tumor growth calculated by caliper and living cell intensity decreased by lenvatinib treatment as analysed by bioluminescence imaging. Phosphorylation of AKT, NF-ĸB, and NF-ĸB downstream proteins involved in tumor progression were reduced by lenvatinib in the tumor tissue. No pathological changes were found in the liver, kidney, and spleen after lenvatinib treatment. Conclusion: Induction of apoptosis and suppression of AKT/NF-ĸB were associated with lenvatinib-induced inhibition of the progression of NSCLC in vivo.Current treatment of advanced non-small cell lung cancer (NSCLC) is guided by the mutation status of driver genes (1). Patients with an actionable driver gene mutation will have longer survival than those carrying no mutation when treated with receptor tyrosine kinase inhibitors (TKIs) (2). However, even with the outstanding efficacy of the third generation TKIs, progression may occur after treatment for approximately 1.5 years (3). The strategy of treatment beyond progression could be based on the identification of actionable acquired driver gene mutations in this population (4).

Humanized PD-1 Knock-in Mice Reveal Nivolumab’s Inhibitory Effects on Glioblastoma Tumor ProgressionIn Vivo

“…in vivo 37: 1991-2000 (2023) 1996 Table IV. Severity scores for pathological alterations after Nivolumab treatment (19).…”

“…On day 29, we collected and isolated serum from each group of mice and stored it at -80˚C. The serums were sent to Bio-Check Laboratories (New Taipei City, Taiwan, ROC) for evaluating Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and gamma-glutamyl transferase (γGT) values using standardized tests (19).…”

The beneficial impact of metabolic dysfunction‐associated fatty liver disease on lenvatinib treatment in patients with non‐viral hepatocellular carcinoma

“…39 In addition, LEN has been reported to induce Akt inactivation, leading to apoptosis and growth inhibition in non-small cell lung cancer in mice. 40 Recent studies have demonstrated the involvement of these molecules in the development of NASH-related HCC. As MAFLD is defined as fatty liver with metabolic dysfunction, we further performed a stratification analysis according to metabolic dysfunction.…”

“…However, LEN is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor and fibroblast growth factor receptor 39 . In addition, LEN has been reported to induce Akt inactivation, leading to apoptosis and growth inhibition in non‐small cell lung cancer in mice 40 . Recent studies have demonstrated the involvement of these molecules in the development of NASH‐related HCC.…”

Quetiapine Significantly Improves the Effectiveness of Radiotherapy in Combating Hepatocellular Carcinoma Progression in a Hep3B Xenograft Mouse Model

“…Alamine aminotransferase (AST), alanine aminotransferease (ALT), creatinine (CREA), and gamma-glutamyl transferase (γ-GT) levels in each serum sample were quantified using analytical services provided by Axel Biotech. Inc. (Taichung, Taiwan, ROC) (29).…”