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Xanthotoxol (Xan), a natural compound extracted from traditional Chinese medicine such as\n                      <jats:italic>Angelica archangelica<\/jats:italic>\n                      , has demonstrated antitumor properties. However, its specific effects on GC remain unreported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hub targets of Xan in GC were identified by integrating weighted gene co\u2010expression network analysis (WGCNA) with network pharmacology. Molecular docking and molecular dynamics (MD) simulations were conducted to analyze the interaction between the hub targets and Xan. The effects of Xan on GC cell proliferation, cell cycle, apoptosis, migration, and invasion were examined using cell experiments and xenograft tumor model. Histopathological evaluation of changes in tumor and liver tissues was performed after Xan intervention. Western blot and reverse transcription quantitative polymerase chain reaction (RT\u2010qPCR) were employed to analyze hub target expression and clarify Xan's molecular mechanism against GC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of six hub genes highly correlated with GC were identified (\n                      <jats:italic>MMP12<\/jats:italic>\n                      ,\n                      <jats:italic>KDR<\/jats:italic>\n                      ,\n                      <jats:italic>CCND1<\/jats:italic>\n                      ,\n                      <jats:italic>PDGFRB<\/jats:italic>\n                      ,\n                      <jats:italic>PLAU<\/jats:italic>\n                      , and\n                      <jats:italic>PLK1<\/jats:italic>\n                      ). Molecular docking and MD simulations revealed a significant binding affinity between Xan and hub genes. Experiments demonstrated that Xan inhibited proliferation, cell cycle, migration, and invasion while promoting apoptosis. Xan could alleviate liver injury caused by subcutaneous tumor in mice. Furthermore, Xan upregulated MMP12 expression and downregulated KDR, CCND1, PDGFRB, PLAU, and PLK1 in GC cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Xan shows promise as a GC treatment by modulating MMP12, KDR, CCND1, PDGFRB, PLAU, and PLK1 expression, which inhibits proliferation, cell cycle, migration, and invasion, while enhancing apoptosis and reducing liver damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70234","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:41:19Z","timestamp":1791607279000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular mechanism of Xanthotoxol against gastric cancer: A comprehensive study integrating network pharmacology, computer simulations, and experimental 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