豆固醇通过调节脂质代谢发挥抗神经胶质瘤的作用。

IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Molecular medicine reports Pub Date : 2024-12-01 Epub Date: 2024-10-04 DOI:10.3892/mmr.2024.13351
Ting Wei, Ruichun Li, Shiwen Guo, Chen Liang
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引用次数: 0

摘要

豆固醇是一种存在于多种中药中的甾醇化合物,但它对胶质瘤的影响尚不清楚。本研究旨在研究豆固醇对胶质母细胞瘤(GBM)细胞生物学行为的影响,并探索其潜在机制。体外实验评估了它对 GBM 细胞增殖、凋亡、细胞周期进展、侵袭、迁移和血管生成模拟(VM)的影响。利用数据库和维恩图分析确定了麦角甾醇治疗 GBM 的潜在靶点,随后使用 R 语言进行了富集分析。通过单变量考克斯回归、最小绝对缩减和选择算子分析,建立了与豆固醇靶基因相关的预后模型。研究发现,豆固醇能以剂量和时间依赖的方式抑制 GBM 细胞的增殖,诱导细胞凋亡,抑制侵袭、迁移和 VM 的形成。此外,还发现了31个豆甾醇的潜在靶点,它们与脂质代谢和G蛋白偶联受体信号通路有关。脂质代谢测定显示,豆固醇能显著降低游离脂肪酸和总胆固醇水平。此外,还筛选出了两个与预后相关的靶基因,即脂肪酸结合蛋白5和α-1B肾上腺素能受体,该预后模型可有效预测GBM的预后。此外,分子对接显示豆固醇与靶蛋白之间有很强的结合亲和力。总之,这些研究结果表明,豆固醇可能通过调节脂质代谢发挥抗胶质瘤的作用。
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Stigmasterol exerts antiglioma effects by regulating lipid metabolism.

Stigmasterol is a sterol compound found in various traditional Chinese medicines; however, its effects on glioma remain unclear. The present study aimed to investigate the effects of stigmasterol on the biological behaviors of glioblastoma (GBM) cells and to explore the underlying mechanisms. In vitro experiments assessed its effects on GBM cell proliferation, apoptosis, cell cycle progression, invasion, migration and vasculogenic mimicry (VM). The potential targets for stigmasterol in treating GBM were identified using databases and Venn diagram analysis, followed by enrichment analysis using R language. A prognostic model related to the target genes of stigmasterol was developed through univariate Cox regression and least absolute shrinkage and selection operator analyses. Stigmasterol was found to suppress the proliferation of GBM cells in a dose‑ and time‑dependent manner, to induce apoptosis, and to inhibit invasion, migration and VM formation. Additionally, 31 potential targets of stigmasterol were identified, linked to lipid metabolism and the G protein‑coupled receptor signaling pathway. Lipid metabolism assays revealed that stigmasterol significantly reduced free fatty acids and total cholesterol levels. Furthermore, two prognosis‑related target genes, fatty acid binding protein 5 and α‑1B adrenergic receptor, were selected, and the prognostic model effectively predicted GBM outcomes. Moreover, molecular docking revealed strong binding affinities between stigmasterol and the target proteins. Overall, these findings suggested that stigmasterol may exert anti‑glioma effects, which could be potentially mediated through the regulation of lipid metabolism.

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来源期刊
Molecular medicine reports
Molecular medicine reports 医学-病理学
CiteScore
7.60
自引率
0.00%
发文量
321
审稿时长
1.5 months
期刊介绍: Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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