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脂肪间充质干细胞条件培养基和提取物:再生乳腺癌治疗的一种有前景的治疗选择。

Adipose mesenchymal stem cell conditioned medium and extract: A promising therapeutic option for regenerative breast cancer therapy.

作者信息

Kazemi Faezeh, Sadeghian Fatemeh, Pirsadeghi Ali, Asadi Fatemeh, Javdani Hossein, Yousefi-Ahmadipour Aliakbar

机构信息

Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Faculty of Paramedicine, Department of Laboratory Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

出版信息

SAGE Open Med. 2024 Dec 16;12:20503121241306606. doi: 10.1177/20503121241306606. eCollection 2024.

DOI:10.1177/20503121241306606
PMID:39691866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11650577/
Abstract

INTRODUCTION

Breast cancer is the second most common cancer and a leading cause of cancer death in U.S. women. The tumor microenvironment, especially nearby adipocytes, plays a crucial role in its progression. Therefore, this study aimed to investigate the effects of human adipose mesenchymal stem cells-derived conditioned medium (SUP) and extract (CE) from on breast cancer cells.

METHODS

Human adipose-derived mesenchymal stem cells were isolated and characterized by flow cytometry using Cluster of Differentiation (CD) markers (CD34, CD45, CD90, and CD105). The differentiation potential was confirmed via adipogenic and osteogenic induction. MCF-7 and MDA-MB-231 cells were treated with SUP and CE, and cell viability was assessed using the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay at 24, 48, and 72 h. Doubling time, colony formation, wound healing, and gene expression for key cancer-related genes (, , , , , , caspase 3, and caspase 9) were also evaluated.

RESULTS

Both SUP and CE significantly inhibited the viability of MCF-7 and MDA-MB-231 cells, reduced their doubling time, and suppressed colony formation. In wound healing assays, cell migration was notably impaired in MDA-MB-231 cells but less so in MCF-7 cells. Real-time polymerase chain reaction revealed downregulation of TIMP1, MMP2, PDL1, and IDO in MDA-MB-231 cells after treatment, while CE increased certain gene expressions in MCF-7 cells. Bax, caspase 3, and caspase 9 expressions were significantly upregulated in MDA-MB-231 cells but not in MCF-7 cells after treatment.

CONCLUSION

Human adipose-derived mesenchymal stem cells-derived SUP and CE exhibit antitumor effects on breast cancer cells, suggesting a potential therapeutic strategy to suppress tumor progression. Mesenchymal stem cells-SUP and CE could be a safe and novel regenerative approach for breast reconstruction postmastectomy without tumor recurrence risk.

摘要

引言

乳腺癌是美国女性中第二常见的癌症,也是癌症死亡的主要原因。肿瘤微环境,尤其是附近的脂肪细胞,在其进展中起着关键作用。因此,本研究旨在探讨人脂肪间充质干细胞条件培养基(SUP)和提取物(CE)对乳腺癌细胞的影响。

方法

分离人脂肪来源的间充质干细胞,并使用分化簇(CD)标志物(CD34、CD45、CD90和CD105)通过流式细胞术进行表征。通过成脂和成骨诱导确认分化潜能。用SUP和CE处理MCF-7和MDA-MB-231细胞,并在24、48和72小时使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法评估细胞活力。还评估了关键癌症相关基因(、、、、、、半胱天冬酶3和半胱天冬酶9)的倍增时间、集落形成、伤口愈合和基因表达。

结果

SUP和CE均显著抑制MCF-7和MDA-MB-231细胞的活力,缩短其倍增时间,并抑制集落形成。在伤口愈合试验中,MDA-MB-231细胞的细胞迁移明显受损,但在MCF-7细胞中受损程度较小。实时聚合酶链反应显示,处理后MDA-MB-231细胞中TIMP1、MMP2、PDL1和IDO表达下调,而CE增加了MCF-7细胞中的某些基因表达。处理后,MDA-MB-231细胞中Bax、半胱天冬酶3和半胱天冬酶9表达显著上调,但MCF-7细胞中未上调。

结论

人脂肪来源的间充质干细胞条件培养基和提取物对乳腺癌细胞具有抗肿瘤作用,提示一种抑制肿瘤进展的潜在治疗策略。间充质干细胞条件培养基和提取物可能是一种安全且新颖的乳房切除术后乳房重建再生方法,无肿瘤复发风险。

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