Abstract：
The electrospun nanofiber system is correlated with high efficacy of drug delivery. This study aims to investigate the effect of nanofiber-based delivery of evodiamine, an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth, on intrahepatic cholangiocarcinoma (ICC), as well as to explore the molecular mechanisms. An electrospun nanofiber system carrying evodiamine was generated. Compared to evodiamine treatment alone, the nano-evodiamine exhibited more pronounced effects on suppressing proliferation, colony formation, invasiveness, migration, apoptosis resistance, cell cycle progression, and in vivo tumorigenesis of two ICC cell lines (HUCC-T1 and RBE). ICC cells exhibited increased expression of histone deacetylase 4 (HDAC4) while decreased tropomyosin 1 (TPM1). HDAC4 suppressed TPM1 expression by removing H3K9ac modifications from its promoter. Nano-evodiamine reduced HDAC4 protein levels in ICC cells, thus promoting transcription and expression of TPM1. Either overexpression of HDAC4 or downregulation of TPM1 negated the tumor-suppressive effects of nano-evodiamine. Collectively, this study demonstrates that the electrospun nanofiber system enhances the efficiency of evodiamine. Additionally, evodiamine suppresses the malignant properties of ICC cells. The findings may provide fresh insights into the application of electrospun nanofiber system for drug delivery and the effects of evodiamine on tumor suppression.
摘要：
电纺纳米纤维系统与药物递送的高功效相关。这项研究旨在研究纳米纤维为基础的传递的效果，一种吲哚生物碱，来自于Rutaceae植物Evodiarutaecarpa（Juss。)Benth,关于肝内胆管癌（ICC），以及探索分子机制。产生了携带evodiamine的电纺纳米纤维系统。与单独使用evodiamine治疗相比，纳米evodiamine表现出更明显的抑制增殖的作用，菌落形成,侵入性,迁移,凋亡抗性，细胞周期进程，以及两种ICC细胞系(HUCC-T1和RBE)的体内肿瘤发生。ICC细胞显示组蛋白脱乙酰酶4（HDAC4）的表达增加，而原肌球蛋白1（TPM1）减少。HDAC4通过从其启动子去除H3K9ac修饰来抑制TPM1表达。纳米evodiamine降低ICC细胞中HDAC4蛋白水平，从而促进TPM1的转录和表达。HDAC4的过表达或TPM1的下调均否定了纳米evodiamine的肿瘤抑制作用。总的来说，这项研究表明，电纺纳米纤维体系提高了吴茱萸胺的效率。此外,evodiamine抑制ICC细胞的恶性特性。这些发现可能为电纺纳米纤维系统在药物递送中的应用以及吴茱萸胺对肿瘤的抑制作用提供新的见解。
