人参皂苷Re通过抑制AMPKα1/STING正反馈环诱导的巨噬细胞M2极化,抑制非小细胞肺癌的进展。

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Phytotherapy Research Pub Date : 2024-11-01 Epub Date: 2024-08-09 DOI:10.1002/ptr.8309
Xiaoyu Tang, Man Zhu, Zeren Zhu, Wenjun Tang, Hongmei Zhang, Yanbin Chen, Feng Liu, Yanmin Zhang
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引用次数: 0

摘要

非小细胞肺癌(NSCLC)中的肿瘤相关巨噬细胞(TAMs)通过与癌细胞相互作用促进肿瘤细胞转移。人参皂苷 Re 能够调节宿主免疫系统,并通过多种途径发挥抗癌作用。AMPK 和 STING 都参与调节 MΦ 极化,从而影响肿瘤的进展。然而,它们之间是否存在调控关系及其对 MΦ 极化和肿瘤进展的影响尚不清楚。本研究旨在提供人参皂苷Re通过抑制AMPKα1/STING正反馈环调节MΦ表型,从而在NSCLC免疫治疗中发挥抗转移作用的机理证据。研究人员构建了细胞培养模型和条件培养基(CM)系统,并通过数据库分析、RT-PCR、Western印迹、流式细胞术和免疫荧光等方法对处理后的MΦ进行分析,以确定AMPK和STING之间的调控关系以及人参皂苷Re对MΦ极化和肿瘤细胞迁移的影响。人参皂苷Re(10、20 mg/kg/天)对小鼠TAMs表型和肿瘤进展的影响通过HE染色、免疫组化染色和Western印迹进行了评估。本研究发现,AMPKα1/STING正反馈环在NSCLC TAMs中诱导M2型极化,进而促进NSCLC细胞迁移。此外,研究还发现人参皂苷Re能抑制M2样MΦ极化,从而抑制NSCLC细胞迁移。从机理上讲,Re能够抑制AMPKα1/STING正反馈环的形成,从而抑制其对M2样MΦ的诱导,进而抑制NSCLC细胞的上皮-间质转化(EMT)过程。此外,在小鼠模型中,Re 还能通过抑制 TAMs 的 M2 型极化来抑制 LLC 肿瘤的生长和定植。我们的研究结果表明,人参皂苷Re能有效调节MΦ极化,从而在NSCLC的抗转移免疫疗法中发挥重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ginsenoside Re inhibits non-small cell lung cancer progression by suppressing macrophage M2 polarization induced by AMPKα1/STING positive feedback loop.

Tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC) promote tumor cell metastasis by interacting with cancer cells. Ginsenoside Re is capable of modulating the host immune system and exerts anticancer effects through multiple pathways. Both AMPK and STING are involved in the regulation of MΦ polarization, thereby affecting tumor progression. However, whether there is a regulatory relationship between them and its effect on MΦ polarization and tumor progression is unclear. The aim of this study was to provide mechanistic evidence that ginsenoside Re modulates MΦ phenotype through inhibition of the AMPKα1/STING positive feedback loop and thus exerts an antimetastatic effect in NSCLC immunotherapy. Cell culture models and conditioned media (CM) systems were constructed, and the treated MΦ were analyzed by database analysis, RT-PCR, Western blotting, flow cytometry, and immunofluorescence to determine the regulatory relationship between AMPK and STING and the effects of ginsenoside Re on MΦ polarization and tumor cells migration. The effects of ginsenoside Re (10, 20 mg/kg/day) on TAMs phenotype as well as tumor progression in mice were assessed by HE staining, immunohistochemical staining, and Western blotting. In this study, AMPKα1/STING positive feedback loop in NSCLC TAMs induced M2 type polarization, which in turn promoted NSCLC cell migration. In addition, ginsenoside Re was discovered to inhibit M2-like MΦ polarization, thereby inhibiting NSCLC cell migration. Mechanistically, Re was able to inhibit the formation of the AMPKα1/STING positive feedback loop, thereby inhibiting its induction of M2-like MΦ and consequently inhibiting the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Furthermore, in mouse models, Re was found to suppress LLC tumor growth and colonization by inhibiting M2-type polarization of TAMs. Our finding indicates that ginsenoside Re can effectively modulate MΦ polarization and thus play an important role in antimetastatic immunotherapy of NSCLC.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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