仑伐替尼通过非小细胞肺癌中的外源性/内源性途径抑制 AKT/NF-κB 信号传导并诱导细胞凋亡。

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

机构信息

Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.

Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.

出版信息

Anticancer Res. 2021 Jan;41(1):123-130. doi: 10.21873/anticanres.14757.

DOI:10.21873/anticanres.14757

PMID:33419805

Abstract

BACKGROUND/AIM: 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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

Altogether, lenvatinib induced extrinsic/intrinsic apoptosis and suppressed migration/invasion ability of NSCLC cells that was associated with AKT/NF-κB signaling inactivation.

摘要

背景/目的：非小细胞肺癌（NSCLC）是一种严重的疾病，也是全球死亡的主要原因。NSCLC 细胞中蛋白激酶 B/核因子-κB（NF-κB）信号转导的过度表达被认为是一种潜在的治疗靶点。仑伐替尼是一种针对血管内皮生长因子受体家族的多激酶抑制剂。然而，仑伐替尼是否可能影响 NSCLC 中的 AKT/NF-κB 尚不清楚。