背景:磺胺是芥子油苷的衍生物,是一种潜在的用于治疗结肠癌的生物活性物质。本研究旨在评价莱芬对人结肠癌Caco-2细胞的潜在抑制作用及其机制。网络药理学,分子对接,并进行了实验验证,以阐明潜在的莱芬治疗这种疾病的机制。
结果:网络药理学预测了莱芬与结肠癌细胞抑制之间的27个交叉靶基因。与结肠癌细胞抑制相关的莱芬靶被鉴定为EGFR,MAPK14,MCL1,GSK3B,PARP1,PTPRC,NOS2,CTSS,TLR9和CTSK。基因本体论功能富集分析表明,上述基因主要与肽酶活性的正向调控有关,炎症反应中的细胞因子产生,和细胞受体信号通路。《京都基因百科全书》和《基因组富集》分析表明,莱芬主要通过影响细胞凋亡以及PD-1、Toll样受体等信号通路抑制癌细胞增殖,T细胞受体,还有P13k-Akt.分子对接结果进一步证实,CTSS、GSK3B,和NOS2显著上调,与莱芬有良好的结合亲和力。体外实验也表明莱芬对人结肠癌Caco-2细胞有明显的抑制作用。
结论:本文首次揭示了莱芬治疗结肠癌的药效学机制。它为莱芬作为药用资源的开发提供了科学见解。©2024化学工业学会。
BACKGROUND: Sulforaphene is a derivative of glucosinolate and a potential bioactive substance used for treating colon cancer. This study aimed to evaluate the potential inhibitory effect and mechanisms of
sulforaphene in human colon cancer Caco-2 cells. Network pharmacology, molecular docking, and experimental verification were performed to elucidate potential sulforaphene mechanisms in the treatment of this condition.
RESULTS: Network pharmacology predicted 27 intersection target genes between
sulforaphene and colon cancer cell inhibition. Key
sulforaphene targets associated with colon cancer cell inhibition were identified as EGFR, MAPK14, MCL1, GSK3B, PARP1, PTPRC, NOS2, CTSS, TLR9, and CTSK. Gene ontology functional enrichment analysis revealed that the above genes were primarily related to the positive regulation of peptidase activity, cytokine production in the inflammatory response, and the cell receptor signaling pathway. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that
sulforaphene mainly inhibited the proliferation of cancer cells by affecting apoptosis as well as the signaling pathways of PD-1, Toll-like receptor, T cell receptor, and P13k-Akt. Molecular docking results further confirmed that CTSS, GSK3B, and NOS2 were significantly up-regulated and had good binding affinity with sulforaphene. In vitro experiments also indicated that sulforaphene had a significant inhibitory effect on human colon cancer Caco-2 cells.
CONCLUSIONS: This paper revealed the pharmacodynamic mechanism of sulforaphene in the treatment of colon cancer for the first time. It provides scientific insight into the development of sulforaphene as a medicinal resource. © 2024 Society of Chemical Industry.