文献类型：期刊文献

英文题名：Network pharmacology analysis and experimental validation of the gastric cancer-related targets of harmine

作者：Hu, Yonghua[1,2,3,4,5,7];Li, Yan[1,5];Wang, Hexin[1,5];Ma, Shujuan[1,5];Liu, Junhong[4];Wei, Qinglin[4];Li, Haiyuan[3,6];Han, Zhijian[2,3];Chen, Hao[2,3,7]

第一作者：呼永华;Hu, Yonghua

通信作者：Hu, YH[1];Hu, YH[2];Chen, H[2];Hu, YH[3];Chen, H[3];Hu, YH[4];Hu, YH[5];Hu, YH[6];Chen, H[6]

机构：[1]Gansu Univ Chinese Med, Affiliated Hosp 2, Sch Clin Med 1, Affiliated Hosp, Lanzhou, Peoples R China;[2]Lanzhou Univ, Hosp 2, Gansu Prov Key Lab Environm Oncol, Lanzhou, Peoples R China;[3]Lanzhou Univ, Clin Med Sch, Lanzhou, Peoples R China;[4]Gansu Univ Chinese Med, Affiliated Hosp, Affiliated Hosp 2, Lanzhou, Peoples R China;[5]Res Ctr Tradit Chinese Med, Lanzhou, Gansu, Peoples R China;[6]Lanzhou Univ, Hosp 2, Dept Tumor Surg, Lanzhou, Peoples R China;[7]Lanzhou Univ, Hosp 2, Lanzhou, Peoples R China

第一机构：甘肃中医药大学第二附属医院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp 2, Sch Clin Med 1, Affiliated Hosp, Lanzhou, Peoples R China;[2]corresponding author), Lanzhou Univ, Hosp 2, Gansu Prov Key Lab Environm Oncol, Lanzhou, Peoples R China;[3]corresponding author), Lanzhou Univ, Clin Med Sch, Lanzhou, Peoples R China;[4]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp, Affiliated Hosp 2, Lanzhou, Peoples R China;[5]corresponding author), Res Ctr Tradit Chinese Med, Lanzhou, Gansu, Peoples R China;[6]corresponding author), Lanzhou Univ, Hosp 2, Lanzhou, Peoples R China.|[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;[10735]甘肃中医药大学;

年份：2026

卷号：16

期号：1

外文期刊名：SCIENTIFIC REPORTS

收录：;Scopus(收录号：2-s2.0-105041369482);WOS:【SCI-EXPANDED(收录号:WOS:001792244600001)】；

基金：This work was supported by the Gansu Provincial Science and Technology Department Key R&D Program - Social Development Project (Grant No. 23YFFA0067), the Gansu University of Chinese Medicine Open Subjects of Gansu Traditional Chinese Medicine Research Center (Grant No.zyzx-2023-15), and the Gansu Provincial Higher Education Innovation Fund Project (Grant No. 2022 A-071), the Lanzhou City Science and Technology Development Plan Project (Grant No. 2021-1-99), the Gansu Provincial Health and Health Industry Research Plan Management Project (Grant No. GSWSKY2020-60), the Research Project on COVID-19 Prevention and Control Technologies (Grant No. 2020-XG-27), the Scientific Research and Innovation Fund Project of Gansu University of Chinese Medicine (Grant No. 2019KC2D-1), the Open Fund Project of the Provincial Key Laboratory for Molecular Medicine and TCM Prevention and Treatment of Major Diseases in Higher Education Institutions in Gansu Province (Grant No. FZYX15-8), the Research Project of Higher Education Institutions in Gansu Province (Grant No. 2016 A-045), the Gansu Provincial Natural Science Foundation (Grant No. 17JR5A169), the Technical Research and Development Special Plan of the Gansu Provincial Department of Science and Technology (Grant No. 1105TCYA019), the Gansu Province Clinical Medicine Research Centers Support Program (Grant Nos. 18JR2FA002 and 21JR7RA682), and the National-Level TCM Superior Specialty Construction Project for Gastroenterology and Ac.

语种：英文

外文关键词：Harmine; Gastric cancer; Network pharmacology analysis; Pull-down assay; HSP90AA1

摘要：Harmine (HM), a natural beta-carboline alkaloid derived from the plant Peganum harmala, has a range of pharmacological effects, including anti-inflammatory, neuroprotective, antidiabetic, and antitumor effects. However, the potential targets involved in its therapeutic effects on gastric cancer (GC) remain unclear. In this study, the anti-gastric cancer effects of HM were investigated and HSP90AA1 was identified as its molecular target. In vitro experiments demonstrated that HM significantly inhibited the proliferation, migration, and invasion of GC cells and induced GC cell apoptosis. By integrating data from multiple databases and from pull-down assays and mass spectrometry analyses, 25 key GC-related targets were identified. A protein-protein interaction (PPI) network was constructed, and ten core targets were prioritized using the maximal clique centrality (MCC) algorithm. Functional enrichment analysis revealed relevant biological processes and pathways, highlighting the multitarget anticancer mechanism of HM. Molecular docking analysis of the interactions between HM and the ten core targets resulted in the selection of heat shock protein 90 alpha family class A member 1 (HSP90AA1) as a candidate for further investigation. Quantitative real-time PCR (RT-qPCR) and Western blot (WB) assays demonstrated that HM treatment significantly decreased the mRNA and protein expression levels of HSP90AA1 in GC cells. Immunofluorescence staining revealed high expression of the HSP90AA1 protein in tumor tissues from the HM-treated group in a mouse xenograft model. The binding affinity between HM and HSP90AA1 was validated as moderate using surface plasmon resonance (SPR) and microscale thermophoresis (MST) assays, further confirming that HSP90AA1 is a key binding target of HM in GC. To elucidate the functional role of HSP90AA1, lentivirus-mediated small interfering RNA (siRNA) was used to generate HSP90AA1-knockdown GC cells, and their functional responses to HM treatment were subsequently examined. The results showed that knockdown of HSP90AA1 inhibited the proliferation, migration, and invasion of GC cells. Combined treatment with HM and HSP90AA1 knockdown further suppressed cell migration, but no significant synergistic effects on proliferation or invasion were observed. In conclusion, the results of this study demonstrate that HM exerts significant anti-GC effects, and HSP90AA1 was identified as a critical binding target that mediates the anti-tumor activity of HM. These findings provide important insights into the potential therapeutic application of HM in GC and support further investigations into personalized treatment strategies.