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聚酰胺-胺/微小RNA-144纳米载体系统通过靶向雷帕霉素靶蛋白信号转导通路抑制胃癌细胞迁移。

PAMAM/miR-144 nanocarrier system inhibits the migration of gastric cancer by targeting mTOR signal transduction pathway.

作者信息

Qian Yayun, Zhu Dongxu, Xu Qiong, Wang Yujie, Chen Xiwen, Hua Weiwei, Xi Juqun, Lu Feng

机构信息

Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225001, China; Department of Pathology, Affiliated Hospital of Yangzhou University, Yangzhou 225001, China.

Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, China.

出版信息

Colloids Surf B Biointerfaces. 2025 May;249:114492. doi: 10.1016/j.colsurfb.2024.114492. Epub 2025 Jan 3.

Abstract

Exogenous microRNA-144 (miR-144) is considered as a potential biological drug for gastric cancer because of its biological activity to inhibit the epithelial-mesenchymal transition (EMT). However, the specific molecular mechanisms have not been fully revealed. In addition, their vulnerability to degradation by RNA enzymes in the blood limits their bioavailability. In this paper, a polyamidoamine (PAMAM)-wrapped miR-144 (PAMAM/miR-144) is prepared as a nanocarrier system to protect miR-144 from nuclease degradation. The PAMAM/miR-144 nanocarrier system achieves the optimal antitumor activity against gastric cancer migration and reduce mTOR protein expression by transferring miR-144 into human gastric cancer HGC-27 cells. At the same time, the PAMAM/miR-144 nanocarrier system significantly decreases the EMT via targeting mTOR signal pathway in HGC-27 cells and noticeably inhibited the growth of subcutaneous gastric cancer xenografts in nude mice. PAMAM/miR-144 nanocarrier system has effectively improved the bioavailability of miR-144, thus providing a promising combination modality for anticancer therapy.

摘要

外源性微小RNA-144(miR-144)因其具有抑制上皮-间质转化(EMT)的生物学活性,被认为是一种潜在的胃癌生物药物。然而,其具体分子机制尚未完全阐明。此外,它们在血液中易被RNA酶降解,这限制了其生物利用度。在本文中,制备了一种聚酰胺-胺(PAMAM)包裹的miR-144(PAMAM/miR-144)作为纳米载体系统,以保护miR-144不被核酸酶降解。PAMAM/miR-144纳米载体系统通过将miR-144导入人胃癌HGC-27细胞,实现了对胃癌迁移的最佳抗肿瘤活性,并降低了mTOR蛋白表达。同时,PAMAM/miR-144纳米载体系统通过靶向HGC-27细胞中的mTOR信号通路显著减少了EMT,并明显抑制了裸鼠皮下胃癌异种移植瘤的生长。PAMAM/miR-144纳米载体系统有效提高了miR-144的生物利用度,从而为抗癌治疗提供了一种有前景的联合治疗方式。

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