Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis

IF 4.2 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Journal of Integrative Medicine-Jim Pub Date : 2025-03-01 DOI:10.1016/j.joim.2025.02.003

Ying-na Chen , Jie-ya Lu , Cheng-feng Gao , Zhi-ruo Fang , Yan Zhou

{"title":"Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis","authors":"Ying-na Chen , Jie-ya Lu , Cheng-feng Gao , Zhi-ruo Fang , Yan Zhou","doi":"10.1016/j.joim.2025.02.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Aloin, the main active component in <em>Aloe vera</em> (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism.</div></div><div><h3>Methods</h3><div>We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.</div></div><div><h3>Results</h3><div>Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.</div><div>Please cite this article as: Chen YN, Lu JY, Gao CF, Fang ZR, Zhou Y. Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis. <em>J Integr Med.</em> 2025; 23(2): 195–208.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 2","pages":"Pages 195-208"},"PeriodicalIF":4.2000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Integrative Medicine-Jim","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2095496425000226","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

Aloin, the main active component in Aloe vera (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism.

Methods

We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.

Results

Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo.

Conclusion

This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.

Please cite this article as: Chen YN, Lu JY, Gao CF, Fang ZR, Zhou Y. Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis. J Integr Med. 2025; 23(2): 195–208.

查看原文本刊更多论文

芦荟素通过调节NR3C2/MT1M轴阻断肺鳞状细胞癌细胞的恶性行为和M2巨噬细胞极化。

目的：研究芦荟中的主要活性成分芦荟素。发热管。F .，已显示出有希望的抗肿瘤作用。本研究探讨芦荟素在肺鳞癌（LUSC）中的作用，并探讨其作用机制。方法：观察芦荟素对2种LUSC细胞株的活力、迁移、侵袭、增殖和凋亡的影响。利用生物信息学方法预测芦荟素的靶分子及下游核受体亚家族3C组成员2 （NR3C2）的靶转录物。测定NR3C2和金属硫蛋白1m （metallothionein 1m, MT1M）在LUSC细胞恶性特性中的生物学功能。建立了LUSC细胞与单核细胞源性巨噬细胞共培养体系。建立小鼠异种移植瘤模型，分析芦荟素和NR3C2在体内对LUSC细胞的致瘤活性和巨噬细胞极化的作用。结果：芦荟素在体外对LUSC细胞的恶性特性有抑制作用。然而，这些影响被NR3C2的沉默所抵消。NR3C2通过结合MT1M启动子激活MT1M转录。MT1M的额外上调抑制了NR3C2沉默增强的LUSC细胞的恶性行为。对巨噬细胞或培养上清中M1和M2标记物/细胞因子的分析显示，aloin处理或MT1M过表达在LUSC细胞中增强了M1极化，抑制了巨噬细胞的M2极化，而NR3C2沉默则导致了相反的趋势。在体内重现了一致的发现。结论：本研究表明芦荟素激活NR3C2/MT1M轴抑制LUSC细胞的恶性行为和M2巨噬细胞极化。陈勇，陆建勇，高春春，方志荣，周勇。芦荟素通过调控NR3C2/MT1M轴抑制肺鳞癌细胞恶性行为及M2巨噬细胞极化。集成医学[J]；打印前Epub。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Integrative Medicine-Jim Medicine-Complementary and Alternative Medicine

CiteScore

9.20

自引率

4.20%

发文量

3319

期刊介绍： The predecessor of JIM is the Journal of Chinese Integrative Medicine (Zhong Xi Yi Jie He Xue Bao). With this new, English-language publication, we are committed to make JIM an international platform for publishing high-quality papers on complementary and alternative medicine (CAM) and an open forum in which the different professions and international scholarly communities can exchange views, share research and their clinical experience, discuss CAM education, and confer about issues and problems in our various disciplines and in CAM as a whole in order to promote integrative medicine. JIM is indexed/abstracted in: MEDLINE/PubMed, ScienceDirect, Emerging Sources Citation Index (ESCI), Scopus, Embase, Chemical Abstracts (CA), CAB Abstracts, EBSCO, WPRIM, JST China, Chinese Science Citation Database (CSCD), and China National Knowledge Infrastructure (CNKI). JIM Editorial Office uses ThomsonReuters ScholarOne Manuscripts as submitting and review system (submission link: http://mc03.manuscriptcentral.com/jcim-en). JIM is published bimonthly. Manuscripts submitted to JIM should be written in English. Article types include but are not limited to randomized controlled and pragmatic trials, translational and patient-centered effectiveness outcome studies, case series and reports, clinical trial protocols, preclinical and basic science studies, systematic reviews and meta-analyses, papers on methodology and CAM history or education, conference proceedings, editorials, commentaries, short communications, book reviews, and letters to the editor. Our purpose is to publish a prestigious international journal for studies in integrative medicine. To achieve this aim, we seek to publish high-quality papers on any aspects of integrative medicine, such as acupuncture and traditional Chinese medicine, Ayurveda medicine, herbal medicine, homeopathy, nutrition, chiropractic, mind-body medicine, taichi, qigong, meditation, and any other modalities of CAM; our commitment to international scope ensures that research and progress from all regions of the world are widely covered. These ensure that articles published in JIM have the maximum exposure to the international scholarly community. JIM can help its authors let their papers reach the widest possible range of readers, and let all those who share an interest in their research field be concerned with their study.