Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer

Abstract

Highlights 1. Apatinib suppressed proliferation, induced cell cycle arrest and apoptosis, and inhibited malignancy in NSCLC in vitro and in vivo. 2. Apatinib downregulated PD-L1 and c-Myc in NSCLC through VEGFR2/STAT3 pathway. 3. Apatinib inhibited PD-L1 expression in THP-1 derived macrophages stimulated by the conditioned medium from NSCLC cells and partially restored the activation of Jurkat T cells co-cultured with NSCLC cells. 4. Apatinib induced ROS generation and inhibited Nrf2 and p62 expression, leading to the autophagic and apoptotic cell death in NSCLC.

Keywords

• NSCLC
• Apatinib
• Apoptosis
• Autophagy
• STAT3/PD-L1
• ROS/Nrf2/p62