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子宫内膜癌细胞来源的诱导外泌体对提取物存在时肿瘤活性的影响。

Effects of Induced Exosomes from Endometrial Cancer Cells on Tumor Activity in the Presence of Extract.

机构信息

Department of Clinical Laboratory Sciences, College of Health Science, Korea University, Seoul 02841, Korea.

Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul 02841, Korea.

出版信息

Molecules. 2021 Apr 12;26(8):2207. doi: 10.3390/molecules26082207.

Abstract

Endometrial cancer (EC) cells metastasize to various regions, including the ovaries, fallopian tubes, cervix, blood, liver, bone, and brain. Various carcinogens are known to cause EC. Exosomes are released from several types of cells and contain various cellular components. In this study, flow cytometry and quantitative PCR were used to evaluate marker levels, cell migration, cell invasion, and mitochondrial membrane potential, and cellular senescence tests were used to estimate cancer activity. The microRNAs were profiled using next-generation sequencing. Although tocopherol-α and rutin content in is high, extract was more useful in modulating tumor activity compared to the two aforementioned substances. Notably, we established that the extract induced bioactive exosomes in EC cells, and profiling of miRNAs in the extract-inducing exosomes (EIE) indicated their potency to be developed as a biological drug. The extract and EIE contributed to the following five biological process categories for EC cells: (1) cell migration and invasion suppression, (2) cellular senescence activation by attenuating mitochondrial membrane potential and enhancing autophagy, (3) reproductive cancer activity attenuation, (4) drug susceptibility activation, and (5) EIE containing miRNAs associated with decreasing inflammation.

摘要

子宫内膜癌 (EC) 细胞转移到各种部位,包括卵巢、输卵管、子宫颈、血液、肝脏、骨骼和大脑。已知各种致癌物质会导致 EC。外泌体由多种类型的细胞释放,包含各种细胞成分。在这项研究中,使用流式细胞术和定量 PCR 来评估标记物水平、细胞迁移、细胞侵袭和线粒体膜电位,以及细胞衰老测试来估计癌症活性。使用下一代测序来分析 microRNAs。尽管 中生育酚-α和芦丁的含量很高,但与上述两种物质相比, 提取物在调节肿瘤活性方面更有用。值得注意的是,我们确定提取物在 EC 细胞中诱导了具有生物活性的外泌体,并且在外泌体诱导的 microRNAs 谱分析 (EIE) 中表明它们有潜力被开发为生物药物。提取物和 EIE 对 EC 细胞的以下五个生物学过程类别有贡献:(1) 抑制细胞迁移和侵袭,(2) 通过降低线粒体膜电位和增强自噬来激活细胞衰老,(3) 减少生殖癌症活性,(4) 激活药物敏感性,以及 (5) 与炎症减轻相关的 EIE 中 microRNAs。

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