{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:59:03Z","timestamp":1790881143457,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is characterized by a poor prognosis, largely driven by metastasis and therapy resistance, processes closely linked to epithelial\u2013mesenchymal transition (EMT) and ferroptosis. Neodymium nitrate (Nd(NO3)3), a predominant neodymium species, has shown antitumor potential, yet its specific effects and underlying mechanisms in HCC remain poorly understood. This study investigated whether Nd(NO3)3 exerts anti-malignant effects in Hep-G2 cells through the Nrf2\u2013ferroptosis axis. We treated Hep-G2 cells with Nd(NO3)3 and assessed proliferation (CCK-8), migration, invasion (wound-healing and Transwell assays), EMT markers (E-cadherin, Vimentin), Nrf2 and GPx4 expression (Western blotting, qRT-PCR), and ferroptosis indicators (ROS, MDA, GSH, Fe2+\/Fe3+). Low-dose Nd(NO3)3 significantly inhibited migration, invasion, and EMT-associated marker expression without affecting proliferation and promoted ferroptotic phenotypes, as evidenced by elevated ROS, MDA, and ferrous iron expression; decreased GSH levels; and downregulated GPx4 expression. Mechanistically, Nd(NO3)3 downregulated Nrf2 expression. Nrf2 overexpression reversed the suppression of migration, invasion, EMT-associated markers, and ferroptotic phenotypes, while the ferroptosis inhibitor deferoxamine rescued migration and invasion. These findings suggest that Nd(NO3)3 exerts anti-malignant effects in Hep-G2 cells by targeting Nrf2 to coordinately suppress EMT and promote ferroptosis, identifying the Nrf2\u2013ferroptosis axis as a potential therapeutic target in HCC cells. However, these findings are based on in vitro experiments in a single Hep-G2 cell line with n = 3 biological replicates, which limits statistical power and generalizability; the results should therefore be interpreted as preliminary evidence requiring further validation in additional cell lines and in vivo models.<\/jats:p>","DOI":"10.3390\/toxics14090831","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:59:41Z","timestamp":1790877581000},"page":"831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neodymium Nitrate Suppresses Malignant Phenotypes in Hep-G2 Cells by Targeting Nrf2 to Inhibit EMT and Induce Ferroptosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Jing","family":"Leng","sequence":"first","affiliation":[{"name":"Institute of Chemical Toxicity Appraisal, National Key Laboratory of Environmental Health Impact Assessment of Environmental New Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5330-2218","authenticated-orcid":false,"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Chemical Toxicity Appraisal, National Key Laboratory of Environmental Health Impact Assessment of Environmental New Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ping","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Chemical Toxicity Appraisal, National Key Laboratory of Environmental Health Impact Assessment of Environmental New Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Xinyu","family":"Hong","sequence":"additional","affiliation":[{"name":"Institute of Chemical Toxicity Appraisal, National Key Laboratory of Environmental Health Impact Assessment of Environmental New Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9092-8958","authenticated-orcid":false,"given":"Song","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Chemical Toxicity Appraisal, National Key Laboratory of Environmental Health Impact Assessment of Environmental New Pollutants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2174\/0113862073439548251029051037","article-title":"Network Pharmacology and Computational Study to Identify Active Components and Potential Targets of Polygonatum sibiricum for Hepatocellular Carcinoma Treatment","volume":"29","author":"Pan","year":"2026","journal-title":"Comb. 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