Cordycepin inhibits glioma growth by downregulating PD-L1 expression via the NOD-like receptor/NFKB1/STAT1 axis.

Autor: Chen J; Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China. Electronic address: jingchen1121@163.com., Liang RS; Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China., Zhuang BB; Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China., Chen HD; Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China., Liu S; Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China., Zhang GL; Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China., Shi SS; Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 Sep 01; Vol. 400, pp. 111178. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1016/j.cbi.2024.111178
Abstrakt: Glioma is a serious primary malignant tumor of the human central nervous system with a poor prognosis and a high recurrence rate; however, inhibition of immune checkpoints can greatly improve the survival rate of patients. The purpose of this study was to investigate the regulation of PD-L1 by cordycepin and the mechanism of its anti-tumor action. The results of previous studies indicate that cordycepin has good anti-proliferative and anti-migratory activities and can induce apoptosis in U251 and T98G cells in vitro. Here, transcriptome sequencing showed that cordycepin may exert anti-tumor effects through the NOD-like receptor signaling pathway. Further intervention with BMS-1, a small molecule inhibitor of PD-L1, was used to explore whether inhibition of PD-L1 affected the regulation of the NOD-like receptor signaling pathway by cordycepin. Mechanistically, on the one hand, cordycepin regulated the expression of NFKB1 and STAT1 through the NOD-like receptor signaling pathway, thereby inhibiting the expression of PD-L1. In addition, inhibition of PD-L1 enhanced the regulation by cordycepin of the NOD-like receptor signaling pathway. On the other hand, cordycepin directly upregulated expression of STAT1 and downregulated that of PD-L1. In vivo studies further showed that cordycepin could downregulate expression of PD-L1 and NFKB1 and upregulate that of STAT1 in glioma xenograft tumor tissues, consistent with the results of in vitro studies. The results suggest that cordycepin may down-regulate the expression of PD-L1 through NOD-like receptor signaling pathway and NFKB signaling pathway, thereby inhibiting the immune escape of glioma, and can be developed as a PD-L1 inhibitor. Our results therefore provide a theoretical foundation for the use of cordycepin in treatment of glioma and enrich our understanding of its pharmacological mechanism.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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