Autophagy-related biological targets and network mechanisms of juglone against bladder cancer.

IF 2.7 3区医学 Q3 ONCOLOGY

Journal of Cancer Research and Clinical Oncology Pub Date : 2025-06-21 DOI:10.1007/s00432-025-06243-5

Yuanfeng Zhang, Enguang Yang, Xinyu Zhang, Ze Zhang, Guoxin Huang, Baoyuan Tang, Chaohu Chen, Longhui Lai, Zixu Pei, Yonghai Zhang, Zhiping Wang

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引用次数: 0

Abstract

Objective: This study aimed to explore juglone's mechanism in inducing autophagy and apoptosis in bladder cancer (BLCA) via network pharmacology and experimental validation.

Methods: Juglone's effects on BLCA cell proliferation, apoptosis, and autophagy were assessed using CCK-8, flow cytometry, transmission electron microscopy, and Western blotting. Network pharmacology, molecular docking, and dynamics simulations identified key targets. In vivo validation employed H&E, immunohistochemical, and TUNEL staining.

Results: Juglone suppressed T24 and UMUC-3 cell proliferation, enhanced autophagy markers, and induced apoptosis. Network analysis identified 108 shared targets, with AKT1, CASP3, and TP53 as core nodes. Pathway enrichment implicated the PI3K/Akt signalling pathway, supported by molecular docking. Autophagy inhibition reduced juglone-induced apoptosis, confirming autophagic death's role.

Conclusions: Juglone triggers BLCA autophagy via PI3K/AKT/mTOR, upregulates apoptotic proteins, and activates caspase 3, promoting apoptosis.

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核桃酮抗膀胱癌的自噬相关生物学靶点及网络机制。

目的：通过网络药理学和实验验证，探讨核桃酮诱导膀胱癌（BLCA）细胞自噬和凋亡的机制。方法：采用CCK-8、流式细胞术、透射电镜、Western blotting检测核桃酮对BLCA细胞增殖、凋亡和自噬的影响。网络药理学、分子对接和动力学模拟确定了关键靶点。体内验证采用H&E、免疫组织化学和TUNEL染色。结果：核桃酮抑制T24和UMUC-3细胞增殖，增强自噬标志物，诱导细胞凋亡。网络分析发现108个共享靶点，其中AKT1、CASP3和TP53为核心节点。通路富集涉及PI3K/Akt信号通路，由分子对接支持。自噬抑制降低了核桃胶酮诱导的细胞凋亡，证实了自噬死亡的作用。结论：核桃酮通过PI3K/AKT/mTOR介导BLCA自噬，上调凋亡蛋白，激活caspase 3，促进细胞凋亡。

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来源期刊

Journal of Cancer Research and Clinical Oncology 医学-肿瘤学

CiteScore

4.00

自引率

2.80%

发文量

577

审稿时长

2 months

期刊介绍： The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.