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

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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.
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