PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■手结膜骨膜。Mazz（虎耳草科）总香豆素（TCPT）在大肠癌（CRC）中显示出抗肿瘤活性，其作用机制未知。外泌体来源的miRNA介导的肿瘤血管生成在CRC转移中对内皮细胞功能具有重要的调节作用。
■研究TCPT对CRC细胞外泌体miRNA表达和血管生成的影响。
■从人类CRC细胞（HT-29）产生HT-29衍生的外泌体，或用TCPT（100μg/mL）处理24小时，然后通过透射电子显微镜进行鉴定，纳米粒子跟踪分析（NTA）和蛋白质印迹。对人脐静脉内皮细胞(HUVECs)和外泌体进行共培养实验,检测外泌体在HUVECs中的摄取及其对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靶miRNA。通过将靶向miRNA的模拟物或抑制剂转染到HUVEC中来进行血管生成的挽救测定。
■HT-29衍生的外泌体，TCPT治疗（Exo-TCPT）后，抑制HUVECs的迁移和管腔形成，降低血管标志物(FLT-1、VCAM-1和VEGFR-2)在HUVECs中的表达水平。此外，miR-375-3p水平在Exo-TCPT中显著上调.拯救实验表明，miR-375-3p在HUVECs中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中表现出抗血管生成，可能通过上调外泌体miR-375-3p。我们的研究结果将揭示新的靶外泌体miRNA介导的肿瘤微环境和结肠膜骨膜在CRC中的治疗应用。
■研究TCPT对CRC细胞外泌体miRNA表达和血管生成的影响。
■从人类CRC细胞（HT-29）产生HT-29衍生的外泌体，或用TCPT（100μg/mL）处理24小时，然后通过透射电子显微镜进行鉴定，纳米粒子跟踪分析（NTA）和蛋白质印迹。对人脐静脉内皮细胞(HUVECs)和外泌体进行共培养实验,检测外泌体在HUVECs中的摄取及其对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靶miRNA。通过将靶向miRNA的模拟物或抑制剂转染到HUVEC中来进行血管生成的挽救测定。
■HT-29衍生的外泌体，TCPT治疗（Exo-TCPT）后，抑制HUVECs的迁移和管腔形成，降低血管标志物(FLT-1、VCAM-1和VEGFR-2)在HUVECs中的表达水平。此外，miR-375-3p水平在Exo-TCPT中显著上调.拯救实验表明，miR-375-3p在HUVECs中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中表现出抗血管生成，可能通过上调外泌体miR-375-3p。我们的研究结果将揭示新的靶外泌体miRNA介导的肿瘤微环境和结肠膜骨膜在CRC中的治疗应用。
