{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:56:37Z","timestamp":1778219797523,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Non\u2010small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9\u2009days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)\u2010mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1\/2, and p\u2010ERK1\/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E\u2010cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E\u2010cadherin, ERK1\/2, and p\u2010ERK1\/2 were detected via qPCR and Western blot. IGF\u20101, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over\u2010expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF\u20101, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p\u2010ERK1\/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p\u2010ERK1\/2 expression, as well as contents of IGF\u20101, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E\u2010cadherin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Glabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1\/2 phosphorylation and suppression of epithelial\u2010mesenchymal transition (EMT).<\/jats:p><\/jats:sec>","DOI":"10.1002\/tox.24235","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T13:08:45Z","timestamp":1711112925000},"page":"412-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulatory mechanism of the Glabrene against non\u2010small cell lung cancer by suppressing 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