ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1600349
This article is part of the Research TopicAdvances in Immunosuppressive Microenvironment Remodeling and Targeted Drug Intervention in Pancreatic CancerView all 3 articles
A glycogen derived from sea urchin-Strongylocentyotus internedius shifts macrophages to the M1 phenotype and enhances the anti-pancreatic cancer activity of gemcitabine
Provisionally accepted
- 1Institute of Oceanology, Chinese Academy of Sciences (CAS), Qingdao, China
- 2National Glycoengineering Research Center, Qingdao, China
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One of the biggest obstacles to treating pancreatic ductal adenocarcinoma (PDAC) is chemotherapy resistance. Macrophages are an essential element of the innate immune system and are distributed in almost every tissue in the body. Among them, macrophages infiltrating into the tumor microenvironment negatively regulate tumor immunity and participate in the generation, invasion, migration and drug resistance of PDAC. In prior study, we isolated a polysaccharide from sea urchin-Strongylocentyotus internedius, which was identified as a high molecular weight, highly branched glycogen (MSGA). In this study, we found that MSGA increased the expression of iNOS, IL-6, TNF α, IL-12 and triggered macrophage differentiation to the CD86+ M1 phenotype. MSGA-induced M1 macrophages decreased the cell viabilities and induced apoptosis of PDAC cells. Additionally, MSGA-polarized M1 macrophages enhanced the pro-apoptosis activity of GEM. Mechanistically, MSGA transformed macrophages to the M1 phenotype through the stimulation of the JAK1/3-STAT1 signaling pathway and the suppression of STAT3 activity. Overall, our research showed that MSGA has profound potential for tumor immunotherapy. And " as an immune stimulator", MSGA could assist gemcitabine in the treatment of PDAC.
Keywords: Glycogen, Tumor Microenvironment, JAK - STAT signaling pathway, gemcitabine, Macrophages
Received: 27 Mar 2025; Accepted: 16 Jun 2025.
Copyright: © 2025 Deng, Yu, Wu, Wang, Wang, Yue, Geng and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ning Wu, Institute of Oceanology, Chinese Academy of Sciences (CAS), Qingdao, China
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