Therapeutic Senolysis of Axitinib-Induced Senescent Human Lung Cancer Cells.

ABSTRACT:

Background

Tyrosine kinase inhibitors (TKIs) inhibit receptor-mediated signals in cells. Axitinib is a TKI with high specificity for vascular endothelial growth factor receptors (VEGFRs).

Aim

We determined whether axitinib could induce senescence in human cancer cells and be lysed by the senolytic drug ABT-263.

Methods

Human lung and breast adenocarcinoma cell lines were used. These cells were cultured with axitinib or a multi-target TKI lenvatinib. The expression of β-galactosidase, VEGFRs, Ki-67, reactive oxygen species (ROS) of cancer cells, and their BrdU uptake were evaluated by flow cytometry. The mRNA expression of p21 and IL-8 was examined by quantitative PCR. The effects of TKIs on phosphorylation of Akt and Erk1/2, as downstream molecules of VEGFR signaling,

SUBMITTER: Kotani H 

PROVIDER: S-EPMC11352446 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature