Yixin Shi , Gengxi Cai , Chuling Zhang , Hong Li , Yichu Nie , Sifei Yu , Beiying Zhang , Moli Wu , Wei Luo , Jia Liu , Zhanwen Guan
{"title":"Resveratrol suppresses growth and VCAN expression in a Cancer-associated fibroblast-breast Cancer hybrid organoid","authors":"Yixin Shi , Gengxi Cai , Chuling Zhang , Hong Li , Yichu Nie , Sifei Yu , Beiying Zhang , Moli Wu , Wei Luo , Jia Liu , Zhanwen Guan","doi":"10.1016/j.intimp.2025.114451","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Cancer-associated fibroblast (CAF) is a major component of the tumor microenvironment (TME) and promotes breast cancer (BC) progression and drug resistance. Two-dimensional cell culture is insufficient to simulate the protective effects of CAFs on tumors, resulting in experimental bias in drug efficacy assays. CAF-organoid co-culture model applied in this study may help solve this problem. Resveratrol (Res) has been found to suppresses BC growth, yet its effects on CAF-protected BC remain unknown.</div></div><div><h3>Methods</h3><div>Surgical resected BC tissues were harvested and established for BC organoids (BCOs, identified with pathological examination) and isolated for CAFs (identified with immunofluorescence) respectively. BCO-CAF co-culture system was established and was measured for the protection effects of CAFs on BCOs. The system was then treated with Res and tested for EdU proliferation assay and calcein-AM/PI viable/non-viable cell labeling. Biogenic analysis was performed and showed that VCAN from CAFs may be important in this process. Versican (VCAN) expression levels in CAFs with or without Res treatment were evaluated by immunohistochemistry, qRT-PCR, and Western blotting.</div></div><div><h3>Results</h3><div>19 BCO cases were successfully cultured and confirmed with pathological examination. Res showed inhibitory effects on 15 of the 19 BCO cases (78.95 %). Although CAFs facilitated organoid growth of BCOs by 69.75 ± 14.78 %, Res treatment eliminated this effect and caused extensive cell death (84.97 % ±5.06 %) in CAF-coated BCOs, accompanied by a decrease in VCAN and TGF-β expression in CAFs.</div></div><div><h3>Conclusions</h3><div>The anti-BC value of Res was further proved by showing its promising suppressive effects on BCOs with or without the presence of CAFs.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114451"},"PeriodicalIF":4.8000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925004412","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Cancer-associated fibroblast (CAF) is a major component of the tumor microenvironment (TME) and promotes breast cancer (BC) progression and drug resistance. Two-dimensional cell culture is insufficient to simulate the protective effects of CAFs on tumors, resulting in experimental bias in drug efficacy assays. CAF-organoid co-culture model applied in this study may help solve this problem. Resveratrol (Res) has been found to suppresses BC growth, yet its effects on CAF-protected BC remain unknown.
Methods
Surgical resected BC tissues were harvested and established for BC organoids (BCOs, identified with pathological examination) and isolated for CAFs (identified with immunofluorescence) respectively. BCO-CAF co-culture system was established and was measured for the protection effects of CAFs on BCOs. The system was then treated with Res and tested for EdU proliferation assay and calcein-AM/PI viable/non-viable cell labeling. Biogenic analysis was performed and showed that VCAN from CAFs may be important in this process. Versican (VCAN) expression levels in CAFs with or without Res treatment were evaluated by immunohistochemistry, qRT-PCR, and Western blotting.
Results
19 BCO cases were successfully cultured and confirmed with pathological examination. Res showed inhibitory effects on 15 of the 19 BCO cases (78.95 %). Although CAFs facilitated organoid growth of BCOs by 69.75 ± 14.78 %, Res treatment eliminated this effect and caused extensive cell death (84.97 % ±5.06 %) in CAF-coated BCOs, accompanied by a decrease in VCAN and TGF-β expression in CAFs.
Conclusions
The anti-BC value of Res was further proved by showing its promising suppressive effects on BCOs with or without the presence of CAFs.
期刊介绍：
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
