研究动态
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乌桕酯P通过促进miR-130b-5p的合成抑制DPP-4表达,从而抑制肺癌的运动能力。

Ugonin P inhibits lung cancer motility by suppressing DPP-4 expression via promoting the synthesis of miR-130b-5p.

发表日期:2023 Sep 11
作者: Chih-Ying Wu, Shubham Suresh Ghule, Chih-Chuang Liaw, David Achudhan, Shuen-Yih Fang, Po-I Liu, Chang-Lun Huang, Ching-Liang Hsieh, Chih-Hsin Tang
来源: Cell Death & Disease

摘要:

肺癌是导致全球癌症相关死亡的主要原因,转移性肺癌的生存率极低。跳毛蓼(Helminthostatchys Zeylanica,简写为H. Zeylanica)是一种中国草药,以其在各种细胞和动物研究中的抗炎、免疫调节和抗癌活性而闻名。本研究评估了H. Zeylanica衍生物对肺癌细胞的影响。我们发现二肽酶-4(DPP-4)在肺癌组织中的表达水平高于正常组织。我们还发现DPP-4在转移期的表达水平更高,并且与肺癌的生存率密切相关。研究显示H. Zeylanica衍生物(乌龙素P)能够以剂量依赖的方式抑制两种肺癌细胞系中DPP-4的mRNA和蛋白表达。乌龙素P能够减少肺癌细胞的迁移和侵袭活性,同时促进miR-130b-5p的合成,后者被发现能够负调控DPP-4蛋白的表达和肺癌细胞的运动能力。我们确定乌龙素P通过下调RAF/MEK/ERK信号通路和增强miR-130b-5p的表达来抑制DPP-4依赖的肺癌细胞迁移和侵袭。本研究提供了有力的证据,表明乌龙素P可能被用于开发治疗肺癌的新型药物。版权所有2023年作者。由Elsevier Masson SAS出版。保留所有权利。
Lung cancer is the leading cause of cancer-related death worldwide, and the survival rate of metastatic lung cancer is exceedingly low. Helminthostatchys Zeylanica (H. Zeylanica) is a Chinese herbal medicine renowned for its anti-inflammatory, immunomodulatory, and anti-cancer activities in various cellular and animal studies. The current study evaluated the effects of H. Zeylanica derivatives on lung cancer cells. We determined that dipeptidyl peptidase-4 (DPP-4) expression levels were higher in lung cancer tissues than in normal tissues. We also determined that DPP-4 expression levels were higher in the metastatic stage and strongly correlated with lung cancer survival rates. An H. Zeylanica derivative (ugonin P) was shown to inhibit DPP-4 mRNA and protein expression in two lung cancer cell lines in a dose-dependent manner. Ugonin P was shown to decrease migration and invasion activities in lung cancer cells while promoting the synthesis of miR-130b-5p, which was found to negatively regulate DPP-4 protein expression and cell motility in lung cancer. We determined that ugonin P suppresses the DPP-4-dependent migration and invasion of lung cancer cells by downregulating the RAF/MEK/ERK signalling pathway and enhancing the expression of miR-130b-5p. This study provides compelling evidence that ugonin P could be used to develop novel therapeutic agents for the treatment of lung cancer.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.