Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells

• 作者: CHEN Xiu-Ping CHEN Yu-Chi FENG Zhe-Ling HUANG Mu-Yang HUANG Run-Yue JIANG Xiao-Ming LIN Li-Gen LIU Bo LU Jin-Jian WANG Yi-Tao YU Hua YUAN Luo-Wei ZHANG Le-Le
• 来源期刊: 中国天然药物
• 学科: 医学
• 年，卷（期）: 2020,（7）
• 页码范围: 517-525
• 页数: 9页
• 分类号: R965
• 语种: 英文
• DOI: 10.1016/S1875-5364(20)30062-5

摘要

Nagilactone E (NLE),a natural product with anticancer activities,is isolated from Podocarpus nagi.In this study,we reported that NLE increased programmed death ligand 1 (PD-L1) expressions at both protein and mRNA levels in human lung cancer cells,and enhanced its localization on the cell membrane.Mechanistically,NLE increased the phosphorylation and expression of c-Jun,and promoted the localization of c-Jun in the nucleus,while silencing of c-Jun by small interfering RNA (siRNA) reduced NLE-induced PD-L1.Further study showed that NLE activated the c-Jun N-terminal kinases (JNK),the upstream of c-Jun,and its inhibitor SP600125 reversed the NLE-increased PD-L 1.Moreover,NLE-induced PD-L1 increased the binding intensity of PD-1 on the cell surface.In summary,NLE upregulates the expression of PD-L1 in lung cancer cells through the activation of JNK-c-Jun axis,which has the potential to combine with the PD-1/PD-L1 antibody therapies in lung cancer.