Pileostegia tomentella 中的总香豆素对结直肠癌细胞外泌体 miRNA 表达和血管生成的影响

IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Pharmaceutical Biology Pub Date : 2024-12-01 Epub Date: 2024-02-12 DOI:10.1080/13880209.2024.2309871
Ying Liu, Dao-Hai Cheng, Zheng-Ying Su, Ji-Hua Lv, Li Wang, Yu-Yin Deng, Li Li
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引用次数: 0

摘要

上下文:Pileostegia tomentella Hand.Mazz(Saxifragaceae)总香豆素(TCPT)对结直肠癌(CRC)具有抗肿瘤活性,但作用机制不明。外泌体衍生的 miRNA 介导的肿瘤血管生成显示了内皮细胞功能在 CRC 转移中的重要调节作用:材料与方法:从人 CRC 细胞(HT-29)或用 TCPT(100 μg/mL)处理 24 小时后产生的 HT-29 衍生外泌体,然后通过透射电子显微镜、纳米颗粒追踪分析(NTA)和 Western 印迹进行鉴定。进行了人脐静脉内皮细胞(HUVECs)和外泌体的共培养实验,以检测外泌体在HUVECs中的吸收及其对HUVECs细胞迁移和管腔形成能力的影响。通过测序技术筛选出外泌体中潜在的目标 miRNA。结果表明:外泌体对HUVECs细胞的迁移和管腔形成能力有影响:结果:HT-29衍生的外泌体经过TCPT处理(Exo-TCPT)后,抑制了HUVECs的迁移和管腔形成,降低了血管标志物(FLT-1、VCAM-1和VEGFR-2)在HUVECs中的表达水平。此外,在 Exo-TCPT 中,miR-375-3p 的水平明显上调。拯救实验表明,HUVECs 中 miR-375-3p 的高表达抑制了迁移和管腔形成能力,这与 Exo-TCPT 的效果一致,而应用 miR-375-3p 抑制剂则显示出相反的效果:TCPT在CRC中具有抗血管生成作用,可能是通过上调外泌体miR-375-3p实现的。我们的研究结果将揭示外泌体 miRNA 介导的肿瘤微环境的新靶点,以及 Pileostegia tomentella 在 CRC 中的治疗应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of total coumarins from Pileostegia tomentella on exosomal miRNA expression and angiogenesis in colorectal cancer cells.

Context: Pileostegia tomentella Hand. Mazz (Saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. Tumour angiogenesis mediated by exosomes-derived miRNA exhibits the vital regulation of endothelial cell function in metastasis of CRC.

Objective: To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.

Materials and methods: HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/mL) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. Co-culture experiments for human umbilical vein endothelial cells (HUVECs) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNAs in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNA into HUVECs.

Results: HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 and VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in Exo-TCPT. Rescue assays showed that high expression of miR-375-3p in HUVECs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects.

Discussion and conclusion: TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of Pileostegia tomentella in CRC.

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来源期刊
Pharmaceutical Biology
Pharmaceutical Biology 医学-药学
CiteScore
6.70
自引率
2.60%
发文量
191
审稿时长
1 months
期刊介绍: Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine. Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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