{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:51:55Z","timestamp":1792173115448,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Department of Science and Technology of Liaoning Province","doi-asserted-by":"publisher","award":["2024\u2010MS\u2010198"],"award-info":[{"award-number":["2024\u2010MS\u2010198"]}],"id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cisplatin (DDP) is a cornerstone chemotherapeutic agent for gastric cancer, yet its clinical application is often limited by severe adverse effects, particularly dose\u2010dependent nephrotoxicity. Quercetin (Que) is a dietary flavonoid widely present in everyday foods such as onions, apples, tea, and broccoli. It has been reported to possess both renoprotective and antitumor properties. This study evaluated the therapeutic potential of combining DDP with Que in gastric cancer treatment. In vitro, CCK\u20108 assays, flow cytometry, and scratch wound tests were employed to assess the impact of Que on DDP\u2010induced nephrotoxicity and chemosensitivity, while potential mechanisms were investigated through western blot analysis. In vivo, the combined regimen was tested in tumor\u2010bearing nude mice by monitoring tumor growth and renal function. Our results showed that Que alleviated DDP\u2010induced suppression of proliferation and apoptosis in HK\u20102 cells, indicating protection against nephrotoxicity. In comparison, in AGS gastric cancer cells, Que potentiated DDP\u2010induced inhibition of proliferation and migration, and improved apoptosis. Mechanistically, Que inhibited ERK1\/2 activation in both cell types. In HK\u20102 cells, ERK1\/2 inhibition increased c\u2010Myc expression and decreased cleaved caspase\u20103 levels, whereas in AGS cells, ERK1\/2 inhibition reduced c\u2010Myc and MMP\u20102 levels while elevating cleaved caspase\u20103 expression. These effects were reversed upon TBHQ treatment. In vivo, Que enhanced the antitumor efficacy of DDP while attenuating its nephrotoxicity. Collectively, these results indicate that Que achieves the abovementioned dual effect via cell type\u2010specific modulation of the ERK1\/2 pathway, supporting its potential as an adjuvant for gastric cancer chemotherapy.<\/jats:p>","DOI":"10.1002\/jbt.71121","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:47:31Z","timestamp":1791200851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quercetin Attenuates Cisplatin\u2010Induced Nephrotoxicity While Enhancing Antitumor Efficacy in Gastric Cancer via Cell Type\u2010Specific Modulation of the ERK1\/2 Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Gen","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Emergency Surgery The First Affiliated Hospital of Jinzhou Medical University Jinzhou China"},{"name":"Key Surgical Laboratory of Educational Administration of Liaoning Province The First 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