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来源于华通氏胶间充质干细胞的外泌体作为紫杉醇的有效药物载体系统,诱导宫颈癌细胞凋亡并抑制 EMT 信号通路。

Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel.

机构信息

Department of Medicinal Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Turkey.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Acibadem University, Istanbul, Turkey.

出版信息

PLoS One. 2022 Sep 15;17(9):e0274607. doi: 10.1371/journal.pone.0274607. eCollection 2022.

Abstract

Mesenchymal stem cells can be obtained and multiplied from various sources and have a very high capacity to release exosomes. Exosomes are nano-sized extracellular vesicles containing biological signaling molecules. This study aimed to determine the effect of MSC-derived exosomes as a drug delivery system for paclitaxel in cervical cancer cells. In this study, human MSC were isolated from wharton jelly of umbilical cord tissue (WJ-MSC), and cells were characterized by CD44, CD90, CD105, and CD34 staining. Exosomes were released in WJ-MSC cells with serum-starved conditions for 48 hours, and particle sizes and structures were examined with zeta-sizer and TEM. In addition, exosomes CD9, CD63, and CD81 markers were checked by western blot. Paclitaxel was loaded into exosomes (Exo-PAC) by electroporation and then incubated with Hela cervical cancer cells for 24 hours. TGF-β, SMAD, Snail, Slug, β-catenin, Notch, Caspase-3, Caspase-9, Bax, Bcl-2 protein and gene expression levels were analyzed in Hela cells. As a result, low concentration Exo-PAC induced apoptosis, and suppressed epithelial-mesenchymal transition proteins in Hela cells. In this study, it has been demonstrated that WJ-MSCs can be used as drug delivery systems for cervical cancer if exosomes are produced scalably in the future.

摘要

间充质干细胞可以从各种来源中获得和扩增,并且具有非常高的释放外泌体的能力。外泌体是一种纳米大小的细胞外囊泡,其中含有生物信号分子。本研究旨在确定 MSC 衍生的外泌体作为紫杉醇在宫颈癌细胞中的药物递送系统的效果。在这项研究中,我们从脐带组织的华通氏胶(WJ-MSC)中分离出人 MSC,并通过 CD44、CD90、CD105 和 CD34 染色对细胞进行鉴定。在血清饥饿条件下将外泌体释放到 WJ-MSC 细胞中 48 小时,并用 zeta-sizer 和 TEM 检查颗粒大小和结构。此外,还通过 Western blot 检查外泌体 CD9、CD63 和 CD81 标志物。通过电穿孔将紫杉醇加载到外泌体(Exo-PAC)中,然后将其与 Hela 宫颈癌细胞共孵育 24 小时。分析了 Hela 细胞中的 TGF-β、SMAD、Snail、Slug、β-catenin、Notch、Caspase-3、Caspase-9、Bax、Bcl-2 蛋白和基因表达水平。结果表明,低浓度的 Exo-PAC 诱导 Hela 细胞凋亡,并抑制上皮-间充质转化蛋白。在这项研究中,如果未来能够规模化生产外泌体,那么 WJ-MSC 可以被用作宫颈癌的药物递送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6721/9477505/2d5b93286609/pone.0274607.g001.jpg

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