Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells.
10.1016/S1875-5364(20)30062-5
- Author:
Yu-Chi CHEN
1
;
Mu-Yang HUANG
1
;
Le-Le ZHANG
2
,
3
;
Zhe-Ling FENG
1
;
Xiao-Ming JIANG
1
;
Luo-Wei YUAN
1
;
Run-Yue HUANG
4
;
Bo LIU
4
;
Hua YU
1
;
Yi-Tao WANG
1
;
Xiu-Ping CHEN
1
;
Li-Gen LIN
1
;
Jin-Jian LU
5
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.
2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
3. School of Medicine, Chengdu University, Chengdu 610106, China.
4. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510120, China.
5. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. Electronic address: jinjianlu@um.edu.mo.
- Publication Type:Journal Article
- Keywords:
JNK;
Lung cancer;
Nagilactone E;
Programmed death ligand 1;
c-Jun
- From:
Chinese Journal of Natural Medicines (English Ed.)
2020;18(7):517-525
- CountryChina
- Language:English
-
Abstract:
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-L1. 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.
