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黄酮类化合物作为胰腺癌 miRNA 表达的调节剂:途径、机制和治疗潜力。

Flavonoids as modulators of miRNA expression in pancreatic cancer: Pathways, Mechanisms, And Therapeutic Potential.

机构信息

Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Sumatera Utara, Indonesia.

Department of Bioscience, Biotechnology and Environment, University of Bari, Bari, Italy.

出版信息

Biomed Pharmacother. 2024 Oct;179:117347. doi: 10.1016/j.biopha.2024.117347. Epub 2024 Sep 5.

DOI:10.1016/j.biopha.2024.117347
PMID:39241569
Abstract

Pancreatic cancer (PC) is a complex malignancy, distinguished by its aggressive characteristics and unfavorable prognosis. Recent developments in understanding the molecular foundations of this disease have brought attention to the noteworthy involvement of microRNAs (miRNAs) in disease development, advancement, and treatment resistance. The anticancer capabilities of flavonoids, which are a wide range of phytochemicals present in fruits and vegetables, have attracted considerable interest because of their ability to regulate miRNA expression. This review provides the effects of flavonoids on miRNA expression in PC, explains the underlying processes, and explores the possible therapeutic benefits of flavonoid-based therapies. Flavonoids inhibit PC cell proliferation, induce apoptosis, and enhance chemosensitivity via the modulation of miRNAs involved in carcinogenesis. Additionally, this review emphasizes the significance of certain miRNAs as targets of flavonoid action. These miRNAs have a role in regulating important signaling pathways such as the phosphoinositide-3-kinase-protein kinase B/Protein kinase B (Akt), mitogen activated protein kinase (MAPK), Janus kinase/signal transducers and activators of transcription (JAK/STAT), and Wnt/β-catenin pathways. This review aims to consolidate current knowledge on the interaction between flavonoids and miRNAs in PC, providing a comprehensive analysis of how flavonoid-mediated modulation of miRNA expression could influence cancer progression and therapy. It highlights the use of flavonoid nanoformulations to enhance stability, increase absorption, and maximize anti-PC activity, improving patient outcomes. The review calls for further research to optimize the use of flavonoid nanoformulations in clinical trials, leading to innovative treatment strategies and more effective approaches for PC.

摘要

胰腺癌(PC)是一种复杂的恶性肿瘤,以其侵袭性特征和不良预后为特征。对这种疾病分子基础的理解的最新进展引起了人们对 microRNAs(miRNAs)在疾病发展、进展和治疗耐药性中的显著作用的关注。黄酮类化合物是水果和蔬菜中存在的一类广泛的植物化学物质,因其能够调节 miRNA 表达而引起了人们的极大兴趣,其具有抗癌能力。

本综述介绍了黄酮类化合物对 PC 中 miRNA 表达的影响,解释了其潜在的作用机制,并探讨了基于黄酮类化合物治疗的可能治疗益处。黄酮类化合物通过调节参与癌变的 miRNA,抑制 PC 细胞增殖、诱导细胞凋亡和增强化学敏感性。

此外,本综述强调了某些 miRNA 作为黄酮类化合物作用靶点的重要性。这些 miRNA 在调节重要信号通路(如磷酸肌醇-3-激酶蛋白激酶 B/蛋白激酶 B(Akt)、丝裂原激活蛋白激酶(MAPK)、Janus 激酶/信号转导和转录激活剂(JAK/STAT)和 Wnt/β-catenin 通路)方面发挥着重要作用。

本综述旨在整合黄酮类化合物与 PC 中 miRNA 之间相互作用的现有知识,全面分析黄酮类化合物介导的 miRNA 表达调节如何影响癌症进展和治疗。它强调了使用黄酮类纳米制剂来提高稳定性、增加吸收和最大化抗 PC 活性,从而改善患者的治疗效果。

该综述呼吁进一步研究,以优化黄酮类纳米制剂在临床试验中的应用,从而为 PC 提供创新的治疗策略和更有效的方法。

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