{"title":"通过飞燕草苷介导的JAK2/STAT3/PD-L1通路抑制三阴性乳腺癌生长","authors":"Xiaoping Yu, Xiaolong Song, Jiali Yan, Ziting Xiong, Lujie Zheng, Yan Luo, Fengcheng Deng, Yanfeng Zhu","doi":"10.29219/fnr.v68.10974","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is a leading cause of cancer-related mortality among women globally, with triple-negative breast cancer (TNBC) being particularly aggressive. Delphinidin (Dp), an anthocyanin monomer, has shown promising health benefits.</p><p><strong>Objective: </strong>This study investigates the effects of Dp on TNBC and aims to elucidate its specific mechanisms of action.</p><p><strong>Design: </strong>We utilized cell counting kit-8 (CCK-8) assays, colony formation assays, and scratch assays to evaluate the influence of Dp on the proliferation and migration of TNBC cells. Flow cytometry was employed to analyze programmed cell death-ligand 1 (PD-L1) and Cluster of Differentiation 69 expression, while Western blotting assessed the levels of PD-L1, Janus Kinase 2 (JAK2), Signal Transducer and Activator of Transcription 3 (STAT3), p-JAK2, p-STAT3, and exosomal marker proteins. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to measure concentrations of PD-L1, interferon-γ (IFN-γ), and tumor necrosis factor-β (TNF-β).</p><p><strong>Results: </strong>Dp effectively inhibited TNBC cell proliferation and migration, as evidenced by CCK-8, colony formation, and scratch assays. Flow cytometry and Western blot analysis indicated a reduction in PD-L1 expression in TNBC cells. Meanwhile, we successfully isolated TNBC cell-derived exosomes, with ELISA experiments showing a decrease in PD-L1 expression in these exosomes following Dp treatment. In a co-culture system with TNBC and Jurkat cells, Dp enhanced Cluster of Differentiation 69 expression and reactivated Jurkat cells, resulting in increased secretion of IFN-γ and TNF-β. Additionally, Dp significantly reduced the p-JAK2/JAK2 and p-STAT3/STAT3 ratios in TNBC cells.</p><p><strong>Conclusion: </strong>Dp may exert its anti-TNBC effects by downregulating PD-L1 expression in TNBC cells and exosomes through the JAK2/STAT3 signaling pathway, potentially restoring T cell activity and modifying the tumor microenvironment.</p>","PeriodicalId":12119,"journal":{"name":"Food & Nutrition Research","volume":"68 ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708511/pdf/","citationCount":"0","resultStr":"{\"title\":\"Inhibition of triple-negative breast cancer growth via delphinidin-mediated suppression of the JAK2/STAT3/PD-L1 pathway.\",\"authors\":\"Xiaoping Yu, Xiaolong Song, Jiali Yan, Ziting Xiong, Lujie Zheng, Yan Luo, Fengcheng Deng, Yanfeng Zhu\",\"doi\":\"10.29219/fnr.v68.10974\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Breast cancer is a leading cause of cancer-related mortality among women globally, with triple-negative breast cancer (TNBC) being particularly aggressive. Delphinidin (Dp), an anthocyanin monomer, has shown promising health benefits.</p><p><strong>Objective: </strong>This study investigates the effects of Dp on TNBC and aims to elucidate its specific mechanisms of action.</p><p><strong>Design: </strong>We utilized cell counting kit-8 (CCK-8) assays, colony formation assays, and scratch assays to evaluate the influence of Dp on the proliferation and migration of TNBC cells. Flow cytometry was employed to analyze programmed cell death-ligand 1 (PD-L1) and Cluster of Differentiation 69 expression, while Western blotting assessed the levels of PD-L1, Janus Kinase 2 (JAK2), Signal Transducer and Activator of Transcription 3 (STAT3), p-JAK2, p-STAT3, and exosomal marker proteins. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to measure concentrations of PD-L1, interferon-γ (IFN-γ), and tumor necrosis factor-β (TNF-β).</p><p><strong>Results: </strong>Dp effectively inhibited TNBC cell proliferation and migration, as evidenced by CCK-8, colony formation, and scratch assays. Flow cytometry and Western blot analysis indicated a reduction in PD-L1 expression in TNBC cells. Meanwhile, we successfully isolated TNBC cell-derived exosomes, with ELISA experiments showing a decrease in PD-L1 expression in these exosomes following Dp treatment. In a co-culture system with TNBC and Jurkat cells, Dp enhanced Cluster of Differentiation 69 expression and reactivated Jurkat cells, resulting in increased secretion of IFN-γ and TNF-β. 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引用次数: 0
摘要
背景：乳腺癌是全球女性癌症相关死亡的主要原因，三阴性乳腺癌（TNBC）尤其具有侵袭性。飞燕草苷（Dp）是一种花青素单体，已显示出良好的健康益处。目的：研究Dp对TNBC的作用，探讨其具体作用机制。设计：采用细胞计数试剂盒-8 （CCK-8）法、菌落形成法和划痕法评估Dp对TNBC细胞增殖和迁移的影响。流式细胞术分析程序性细胞死亡配体1 （PD-L1）和分化簇69的表达，Western blotting检测PD-L1、Janus Kinase 2 （JAK2）、Signal Transducer and Activator of Transcription 3 （STAT3）、p-JAK2、p-STAT3和外泌体标记蛋白的水平。此外，采用酶联免疫吸附试验（ELISA）测定PD-L1、干扰素-γ (IFN-γ)和肿瘤坏死因子-β (TNF-β)的浓度。结果：Dp有效抑制TNBC细胞增殖和迁移，CCK-8、菌落形成和划痕实验均证实了这一点。流式细胞术和Western blot分析显示TNBC细胞中PD-L1表达降低。同时，我们成功分离了TNBC细胞来源的外泌体，ELISA实验显示Dp处理后这些外泌体中的PD-L1表达降低。在与TNBC和Jurkat细胞共培养的系统中，Dp增强了Cluster of Differentiation 69的表达并重新激活Jurkat细胞，导致IFN-γ和TNF-β的分泌增加。此外，Dp显著降低TNBC细胞中p-JAK2/JAK2和p-STAT3/STAT3比值。结论：Dp可能通过JAK2/STAT3信号通路下调TNBC细胞和外泌体中PD-L1的表达，可能恢复T细胞活性，改变肿瘤微环境，从而发挥其抗TNBC作用。
Inhibition of triple-negative breast cancer growth via delphinidin-mediated suppression of the JAK2/STAT3/PD-L1 pathway.
Background: Breast cancer is a leading cause of cancer-related mortality among women globally, with triple-negative breast cancer (TNBC) being particularly aggressive. Delphinidin (Dp), an anthocyanin monomer, has shown promising health benefits.
Objective: This study investigates the effects of Dp on TNBC and aims to elucidate its specific mechanisms of action.
Design: We utilized cell counting kit-8 (CCK-8) assays, colony formation assays, and scratch assays to evaluate the influence of Dp on the proliferation and migration of TNBC cells. Flow cytometry was employed to analyze programmed cell death-ligand 1 (PD-L1) and Cluster of Differentiation 69 expression, while Western blotting assessed the levels of PD-L1, Janus Kinase 2 (JAK2), Signal Transducer and Activator of Transcription 3 (STAT3), p-JAK2, p-STAT3, and exosomal marker proteins. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to measure concentrations of PD-L1, interferon-γ (IFN-γ), and tumor necrosis factor-β (TNF-β).
Results: Dp effectively inhibited TNBC cell proliferation and migration, as evidenced by CCK-8, colony formation, and scratch assays. Flow cytometry and Western blot analysis indicated a reduction in PD-L1 expression in TNBC cells. Meanwhile, we successfully isolated TNBC cell-derived exosomes, with ELISA experiments showing a decrease in PD-L1 expression in these exosomes following Dp treatment. In a co-culture system with TNBC and Jurkat cells, Dp enhanced Cluster of Differentiation 69 expression and reactivated Jurkat cells, resulting in increased secretion of IFN-γ and TNF-β. Additionally, Dp significantly reduced the p-JAK2/JAK2 and p-STAT3/STAT3 ratios in TNBC cells.
Conclusion: Dp may exert its anti-TNBC effects by downregulating PD-L1 expression in TNBC cells and exosomes through the JAK2/STAT3 signaling pathway, potentially restoring T cell activity and modifying the tumor microenvironment.
期刊介绍：
Food & Nutrition Research is a peer-reviewed journal that presents the latest scientific research in various fields focusing on human nutrition. The journal publishes both quantitative and qualitative research papers.
Through an Open Access publishing model, Food & Nutrition Research opens an important forum for researchers from academic and private arenas to exchange the latest results from research on human nutrition in a broad sense, both original papers and reviews, including:
* Associations and effects of foods and nutrients on health
* Dietary patterns and health
* Molecular nutrition
* Health claims on foods
* Nutrition and cognitive functions
* Nutritional effects of food composition and processing
* Nutrition in developing countries
* Animal and in vitro models with clear relevance for human nutrition
* Nutrition and the Environment
* Food and Nutrition Education
* Nutrition and Economics
Research papers on food chemistry (focus on chemical composition and analysis of foods) are generally not considered eligible, unless the results have a clear impact on human nutrition.
The journal focuses on the different aspects of nutrition for people involved in nutrition research such as Dentists, Dieticians, Medical doctors, Nutritionists, Teachers, Journalists and Manufacturers in the food and pharmaceutical industries.
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