研究动态
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姜黄素治疗胃癌:通过网络药理学、对接和体外实验进行机制预测。

Curcumin for gastric cancer: Mechanism prediction via network pharmacology, docking, and in vitro experiments.

发表日期:2024 Aug 15
作者: Peng-Hui Yang, Ya-Nan Wei, Bi-Juan Xiao, Si-Yi Li, Xin-Long Li, Liang-Jun Yang, Hua-Feng Pan, Geng-Xin Chen
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

姜黄素源自天然草药姜黄,其抗肿瘤作用早已为人所知。然而,姜黄素影响胃癌(GC)的机制尚未阐明。为了阐明姜黄素治疗GC的潜在机制,采用网络药理学方法对姜黄素进行网络分析。我们首先分析了利平斯基五法则对于姜黄素的使用。使用 PharmMapper、SwissTargetPrediction 和 DrugBank 网络数据库预测姜黄素潜在靶标。 GC 疾病目标是通过 GeneCard、OMIM、DrugBank 和 TTD 网络数据库挖掘的。然后进行GO富集、KEGG富集、蛋白质-蛋白质相互作用(PPI)和总体生存分析。通过分子对接、差异表达分析和细胞实验进一步验证了结果。我们总共鉴定了48个姜黄素相关基因和31个重叠的GC相关靶点。姜黄素和 GC 之间的交叉靶标已丰富到 81 个 GO 生物过程和 22 个重要途径。 PPI 分析后,确定了 6 个中枢靶点,即雌激素受体 1 (ESR1)、表皮生长因子受体 (EGFR)、细胞色素 P450 家族 3 亚家族 A 成员 4 (CYP3A4)、丝裂原激活蛋白激酶 14 (MAPK14)、细胞色素P450 家族 1 亚家族 A 成员 2 (CYP1A2) 和细胞色素 p450 家族 2 亚家族 B 成员 6 (CYP2B6)。这些因素与诊断为 GC 的患者生存率下降相关。分子对接分析进一步证实了姜黄素与枢纽靶基因之间的强结合相互作用。实验结果表明,姜黄素不仅能有效抑制BGC-823细胞的生长,还能抑制其增殖。 BGC-823细胞中中枢靶点CYP3A4、MAPK14、CYP1A2和CYP2B6的mRNA水平在各剂量组中均显着增加。姜黄素可以通过多种靶点、途径和生物过程发挥抗GC作用。©作者)2024年。百事登出版集团有限公司出版。版权所有。
Curcumin originates from the natural herb turmeric, and its antitumor effects have been known about for a long time. However, the mechanism by which curcumin affects gastric cancer (GC) has not been elucidated.To elucidate the potential mechanisms of curcumin in the treatment of GC.Network pharmacological approaches were used to perform network analysis of Curcumin. We first analyzed Lipinski's Rule of Five for the use of Curcumin. Curcumin latent targets were predicted using the PharmMapper, SwissTargetPrediction and DrugBank network databases. GC disease targets were mined through the GeneCard, OMIM, DrugBank and TTD network databases. Then, GO enrichment, KEGG enrichment, protein-protein interaction (PPI), and overall survival analyses were performed. The results were further verified through molecular docking, differential expression analysis and cell experiments.We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets. The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways. Following PPI analysis, 6 hub targets were identified, namely, estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), mitogen-activated protein kinase 14 (MAPK14), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), and cytochrome p450 family 2 subfamily B member 6 (CYP2B6). These factors are correlated with decreased survival rates among patients diagnosed with GC. Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes. The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation. mRNA levels of hub targets CYP3A4, MAPK14, CYP1A2, and CYP2B6 in BGC-823 cells were significantly increased in each dose group.Curcumin can play an anti-GC role through a variety of targets, pathways and biological processes.©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.