黄芪茯苓汤通过肿瘤坏死因子信号通路抑制胃癌的侵袭和转移。

Huangqi fuling decoction inhibits the invasion and metastasis of gastric cancer via the TNF signaling pathway.

作者信息

Luo Yanhai, Ruan Jianqiao, Zhang Junfei, Zhang Simin, Zhang Minghui, Tian Yuan, Wang Wenyi, Wang Jiali, Ma Cunyan, Wang Jing

机构信息

Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan, 750000, Ningxia, China.

Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, 750000, Ningxia, China.

出版信息

Sci Rep. 2025 Jun 4;15(1):19628. doi: 10.1038/s41598-025-00920-8.

Abstract

Gastric cancer (GC) is a prevalent digestive tract malignancy, and Huangqi Fuling decoction (HF) has shown potential in enhancing immune function and exhibiting anti-GC activity. However, its mechanisms remain unclear. This study utilized network pharmacology, molecular docking, and in vitro experiments to preliminarily explore the mechanisms by which HF inhibits gastric cancer invasion and metastasis while promoting apoptosis. Public databases identified differentially expressed genes (DEGs), HF targets, and GC-related genes. GO and KEGG analyses revealed signaling pathways. Clinical relevance, immune infiltration, immunotherapy, and molecular docking of hub genes were analyzed. Eight hub genes-PTGS2, MMP9, SELE, CCL2, VCAM1, ICAM1, CXCL2, and CXCL10-associated with the TNF signaling pathway were identified. HF inhibits the invasion and metastasis of GC cells by down-regulating MMP9 and PTGS2 expression, while inducing apoptosis by suppressing BCL-2 expression and promoting BAX expression. Additionally, HF can arrest the cell cycle, blocking AGS cells in the S phase and HGC-27 cells in the G0/G1 phase. This study confirms that HF promotes apoptosis and inhibits metastasis and invasion in GC cells, primarily by modulating the TNF signaling pathway. Additionally, the anti-tumor effects of HF on GC may involve immune regulatory mechanisms, but the mechanism require further experimental verification.

摘要

胃癌(GC)是一种常见的消化道恶性肿瘤,黄芪茯苓汤(HF)在增强免疫功能和展现抗GC活性方面已显示出潜力。然而,其机制仍不清楚。本研究利用网络药理学、分子对接和体外实验,初步探索HF抑制胃癌侵袭和转移同时促进细胞凋亡的机制。公共数据库鉴定出差异表达基因(DEG)、HF靶点和GC相关基因。基因本体(GO)和京都基因与基因组百科全书(KEGG)分析揭示了信号通路。对枢纽基因的临床相关性、免疫浸润、免疫治疗和分子对接进行了分析。鉴定出8个与肿瘤坏死因子(TNF)信号通路相关的枢纽基因——环氧化酶2(PTGS2)、基质金属蛋白酶9(MMP9)、选择素E(SELE)、趋化因子配体2(CCL2)、血管细胞黏附分子1(VCAM1)、细胞间黏附分子1(ICAM1)、趋化因子CXCL2和趋化因子CXCL10。HF通过下调MMP9和PTGS2表达抑制GC细胞的侵袭和转移,同时通过抑制B细胞淋巴瘤-2(BCL-2)表达和促进Bax蛋白(BAX)表达诱导细胞凋亡。此外,HF可使细胞周期停滞,将AGS细胞阻滞在S期,将人胃癌细胞系HGC-27细胞阻滞在G0/G1期。本研究证实,HF主要通过调节TNF信号通路促进GC细胞凋亡并抑制其转移和侵袭。此外,HF对GC的抗肿瘤作用可能涉及免疫调节机制,但该机制需要进一步的实验验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf59/12137655/b6675e4aad19/41598_2025_920_Fig1_HTML.jpg

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