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While cisplatin (CDDP) is a first-line chemotherapy for NSCLC, its clinical utility is limited by toxicity, drug resistance, and inadequate tumor suppression. Plant-derived extracts have shown promise as complementary therapies, offering potential benefits including enhanced efficacy and reduced treatment side effects. The aqueous extract of Actinidia eriantha Benth. root (WE-AER) exhibits significant antitumor activity, though its mechanisms in NSCLC remain unclear. This study demonstrates WE-AER\u2019s potent anti-NSCLC effects through multiple mechanisms. In vitro, WE-AER dose-dependently inhibited A549 cell growth (74.74% inhibition, IC50 = 210.38 \u00b5g\/mL) by inducing apoptosis via TGF-\u03b2\/FOXO\/mTOR pathway modulation. In vivo, WE-AER suppressed tumor growth and angiogenesis while activating immune responses and reducing inflammation in mouse models, with excellent biosafety. These findings elucidate WE-AER\u2019s anticancer mechanisms and support its potential as a novel herbal therapy for NSCLC.<\/jats:p>","DOI":"10.3390\/ijms26188957","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:56:46Z","timestamp":1758013006000},"page":"8957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Actinidia eriantha Benth. Root as a New Phytomedicine Inhibits Non-Small Cell Lung Cancer by Regulating\u00b7TGF-\u03b2\/FOXO\/mTOR"],"prefix":"10.3390","volume":"26","author":[{"given":"Xuan","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China"},{"name":"Jinhua Institute, Zhejiang University, Jinhua 321299, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiyao","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoran","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoming","family":"Yang","sequence":"additional","affiliation":[{"name":"Longquan Industrial Innovation Research Institute, Zhejiang University, Longquan 323700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingli","family":"Li","sequence":"additional","affiliation":[{"name":"Longquan Industrial Innovation Research Institute, Zhejiang University, Longquan 323700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9763-383X","authenticated-orcid":false,"given":"Lihua","family":"Peng","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China"},{"name":"Jinhua Institute, Zhejiang University, Jinhua 321299, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. 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