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桑色素抑制鼻咽癌生长治疗机制的网络药理学及生物学验证

Network pharmacology and biological verification of morusin's therapeutic mechanisms in inhibiting nasopharyngeal carcinoma growth.

作者信息

Peng Zhang, Hong Ran, Dunhui Yang, Zhen Wang, Yongjin Wu, Xianhai Zeng

机构信息

Department of Otolaryngology, Longgang Otolaryngology Hospital & Shenzhen Key Laboratory of Otolaryngology, Shenzhen Institute of Otolaryngology, Shenzhen, Guangdong, China.

出版信息

J Cancer. 2024 Jul 16;15(15):4866-4878. doi: 10.7150/jca.97044. eCollection 2024.

Abstract

Nasopharyngeal carcinoma (NPC) presents a significant therapeutic challenge due to its aggressive nature and limited treatment options. Although morusin, a compound found in traditional Chinese medicines, exhibits significant tumor-inhibiting properties, its specific effects on NPC proliferation remain unclear. This study aims to elucidate the inhibitory effects of morusin on NPC survival and proliferation while exploring the underlying mechanisms through the utilization of network pharmacology, molecular docking, and experimental validation and . Network pharmacology analysis identified 117 potential targets of morusin against NPC, with 8 hub targets including AKT1, BCL2, CASP3, CTNNB1, ESR1, HSP90AA1, MMP9, STAT3, and the IL-17 signaling pathway. Further investigation of public data indicated that the expression levels of BLC2, CASP3, CTNNB1, HSP90AA1, and STAT3 in NPC tissue were significantly elevated compared to normal nasopharyngeal tissue. Docking studies exposed robust binding activity between morusin and key gene molecules. Additionally, biological assays demonstrated that morusin effectively inhibits NPC growth both and . Through a comprehensive investigation, this study identified the pharmacological mechanisms essential for morusin-induced inhibition of NPC growth by targeting multiple molecular targets and signaling pathways. These findings show the potential to contribute to the development of novel clinical agents for treating NPC.

摘要

鼻咽癌(NPC)因其侵袭性本质和有限的治疗选择而带来了重大的治疗挑战。尽管桑色素是一种在传统中药中发现的化合物,具有显著的肿瘤抑制特性,但其对鼻咽癌增殖的具体作用仍不清楚。本研究旨在阐明桑色素对鼻咽癌存活和增殖的抑制作用,同时通过网络药理学、分子对接和实验验证来探索其潜在机制。网络药理学分析确定了桑色素针对鼻咽癌的117个潜在靶点,其中包括AKT1、BCL2、CASP3、CTNNB1、ESR1、HSP90AA1、MMP9、STAT3等8个核心靶点以及IL-17信号通路。对公开数据的进一步研究表明,与正常鼻咽组织相比,鼻咽癌组织中BLC2、CASP3、CTNNB1、HSP90AA1和STAT3的表达水平显著升高。对接研究揭示了桑色素与关键基因分子之间的强结合活性。此外,生物学试验表明桑色素在体内和体外均能有效抑制鼻咽癌的生长。通过全面研究,本研究确定了桑色素通过靶向多个分子靶点和信号通路诱导抑制鼻咽癌生长所必需的药理机制。这些发现显示了有助于开发治疗鼻咽癌的新型临床药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9732/11310868/9cf43bf8b97e/jcav15p4866g001.jpg

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