n/a
Abstract Title:

Shikonin-mediated PD-L1 degradation suppresses immune evasion in pancreatic cancer by inhibiting NF-κB/STAT3 and NF-κB/CSN5 signaling pathways.

Abstract Source:

Pancreatology. 2021 Apr ;21(3):630-641. Epub 2021 Feb 12. PMID: 33707115

Abstract Author(s):

Zhiyan Ruan, Minhua Liang, Ling Shang, Manxiang Lai, Xiangliang Deng, Xinguo Su

Article Affiliation:

Zhiyan Ruan

Abstract:

BACKGROUND: Pancreatic cancer (PC) is a highly fatal malignancy with few effective therapies currently available. Recent studies have shown that PD-L1 inhibitors could be potential therapeutic targets for the treatment of PC. The present study aims to investigate the effect of Shikonin on immune evasion in PC with the involvement of the PD-L1 degradation.

METHODS: Initially, the expression patterns of PD-L1 and NF-κB in PC were predicted in-silico using the GEPIA database, and were subsequently validated using PC tissues. Thereafter, the correlation of NF-κB with STAT3, CSN5 and PD-L1 was examined. PC cells were treated with Shikonin, NF-κB inhibitor, STAT3 activator, and CSN5 overexpression plasmid to investigate effects on PD-L1 glycosylation and immune evasion in PC. Finally, in vivo tumor formation was induced in C57BL/6J mice, in order to verify the in vitro results.

RESULTS: PD-L1, NF-κB, NF-κB p65, STAT3, and CSN5 were highly expressed in PC samples, and NF-κB was positively correlated with STAT3/CSN5/PD-L1. Inhibition of NF-κB decreased PD-L1 glycosylation and increased PD-L1 degradation, whereas activated STAT3 and overexpressed CSN5 reversed these trends. Shikonin blockedimmune evasion in PC, and lowered the expression of PD-L1, NF-κB, NF-κB p65, STAT3 and CSN5 in vivo and in vitro.

CONCLUSION: The findings indicated Shikonin inhibited immune evasion in PC by inhibiting PD-L1 glycosylation and activating the NF-κB/STAT3 and NF-κB/CSN5 signaling pathways. These effects of Shikonin on PC cells may bear important potential therapeutic implications for the treatment of PC.

Study Type : Animal Study, In Vitro Study

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2022 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.