ArticleNaunyn-Schmiedeberg's archives of pharmacology2026
Paeoniflorin's role in inhibiting malignant metastasis of gastrointestinal stromal tumors via CYP3A4 modulation.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Gastrointestinal stromal tumors (GIST) can become malignant upon recurrence and metastasis, yet no drugs specifically target these processes. This study explores the effectiveness and mechanism of paeoniflorin in treating GIST. Initially, the impact of paeoniflorin on the viability, proliferation, and migration of GIST cell lines (GIST-T1 and GIST-882) was assessed using CCK-8, transwell, and wound healing assays at low (5 μM) and high (20 μM) concentrations. Subsequently, datasets GSE136755 and GSE21315 were analyzed to identify potential therapeutic targets for inhibiting GIST transfer. Key genes and pathways related to Paeoniflorin's anti-GIST effects were identified through molecular docking and Western blotting. Paeoniflorin influenced cell viability, proliferation, and migration in GIST-T1 and GIST-882 cell lines at low (5 μM) and high (20 μM) concentrations. We identified 761 differentially expressed genes (DEGs) and selected 50 hub genes using a PPI network. By screening paeoniflorin's potential targets, we identified eight key genes (CYP1A2, CYP2C9, CYP3A4, F2, ICAM1, NR1H4, PLG, and SERPINE1) that were significantly elevated in metastatic GIST samples. CYP3A4 was confirmed as a target of Paeoniflorin in GIST treatment through molecular docking and Western blotting. Pan-cancer analysis showed CYP3A4's enrichment in the tight junction pathway and a significant negative correlation with AKT2 protein. Paeoniflorin treatment led to high AKT2 expression in the tight junction pathway in GIST cell lines. Paeoniflorin acts on the CYP3A4 protein to affect the tight junction pathway, inhibiting the malignant metastasis of GIST.
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