Doxorubicin loaded exosomes inhibit cancer-associated fibroblasts growth: in vitro and in vivo study.

IF 6 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2025-02-27 DOI:10.1186/s12935-025-03689-y

Fatemeh Akhavan Attar, Shiva Irani, Mana Oloomi, Azam Bolhassani, Loabat Geranpayeh, Fatemeh Atyabi

{"title":"Doxorubicin loaded exosomes inhibit cancer-associated fibroblasts growth: in vitro and in vivo study.","authors":"Fatemeh Akhavan Attar, Shiva Irani, Mana Oloomi, Azam Bolhassani, Loabat Geranpayeh, Fatemeh Atyabi","doi":"10.1186/s12935-025-03689-y","DOIUrl":null,"url":null,"abstract":"<p><p>Cancer-associated fibroblast cells (CAFs) play a key role in the breast cancer (BC) microenvironment that induces resistance to chemotherapy. Adipose mesenchymal stem cells (ADMSCs) derived exosomes were utilized to deliver the doxorubicin (Dox) to BC cell lines (MDA-MB-231, MCF-7) and CAFs in both mono and co-culture systems. Immunocytochemistry (ICC) for VIMENTIN and flow cytometry for the CD45, CD34, CD73, and CD90 markers were used to confirm the phenotypic characteristics of CAFs and MSC cells. Dox was loaded into ADMSCs-derived exosomes (Exo-Dox) through sonication and its loading wasa confirmed by transmission electron microscope (TEM). Compared to free Dox, Exo-Dox showed a higher efficiency in inducing apoptosis and inhibiting growth and migration in co-culture cells with CAFs (P < 0.05). The up-regulation of H19 and UCA1 lncRNAs, associated with chemoresistance, was confirmed using real-time PCR in CAF-derived breast cancer patients, CAF-derived exosomes, and exosome-derived patient serums. H19 and UCA1 expression levels were significantly down-regulated in MDA-MB-231, MCF-7, and co-cultures of MDA-MB-231 and MCF-7 cells with CAFs that received Exo-Dox treatment. In vivo results indicated that ADMSCs-derived exosomes (MSC-Exos) can accumulate at the tumor site. Exo-Dox suppressed cancer cell growth and significantly decreased tumor size compared to PBS (p < 0.01). The findings confirmed the growth inhibition effects of Exo-Dox n in CAFs, BC cells, and tumor-bearing mice.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"72"},"PeriodicalIF":6.0000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869484/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03689-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Cancer-associated fibroblast cells (CAFs) play a key role in the breast cancer (BC) microenvironment that induces resistance to chemotherapy. Adipose mesenchymal stem cells (ADMSCs) derived exosomes were utilized to deliver the doxorubicin (Dox) to BC cell lines (MDA-MB-231, MCF-7) and CAFs in both mono and co-culture systems. Immunocytochemistry (ICC) for VIMENTIN and flow cytometry for the CD45, CD34, CD73, and CD90 markers were used to confirm the phenotypic characteristics of CAFs and MSC cells. Dox was loaded into ADMSCs-derived exosomes (Exo-Dox) through sonication and its loading wasa confirmed by transmission electron microscope (TEM). Compared to free Dox, Exo-Dox showed a higher efficiency in inducing apoptosis and inhibiting growth and migration in co-culture cells with CAFs (P < 0.05). The up-regulation of H19 and UCA1 lncRNAs, associated with chemoresistance, was confirmed using real-time PCR in CAF-derived breast cancer patients, CAF-derived exosomes, and exosome-derived patient serums. H19 and UCA1 expression levels were significantly down-regulated in MDA-MB-231, MCF-7, and co-cultures of MDA-MB-231 and MCF-7 cells with CAFs that received Exo-Dox treatment. In vivo results indicated that ADMSCs-derived exosomes (MSC-Exos) can accumulate at the tumor site. Exo-Dox suppressed cancer cell growth and significantly decreased tumor size compared to PBS (p < 0.01). The findings confirmed the growth inhibition effects of Exo-Dox n in CAFs, BC cells, and tumor-bearing mice.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

负载阿霉素的外泌体抑制癌症相关成纤维细胞生长：体外和体内研究。

癌症相关成纤维细胞（CAFs）在诱导化疗耐药的乳腺癌（BC）微环境中起关键作用。利用脂肪间充质干细胞（ADMSCs）衍生的外泌体在单培养和共培养系统中向BC细胞系（MDA-MB-231, MCF-7）和CAFs输送阿霉素（Dox）。免疫细胞化学（ICC）检测VIMENTIN，流式细胞术检测CD45、CD34、CD73和CD90标记物，以确定CAFs和MSC细胞的表型特征。通过超声将Dox装载到admscs衍生的外泌体（Exo-Dox）中，并通过透射电镜（TEM）证实其装载。与游离Dox相比，Exo-Dox在诱导细胞凋亡、抑制细胞生长和迁移方面表现出更高的效率(P

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分钟内获得全文去求助

来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.