{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:25:47Z","timestamp":1787099147409,"version":"build-2736575974"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to elucidate the molecular mechanisms by which Polyphyllin I (PPI), a potent steroidal saponin, attenuates non\u2010small cell lung cancer (NSCLC) progression via mechanistic reprogramming of an autophagy\u2010dependent immunogenic response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Integrated in\u00a0vitro (A549, H460) and in\u00a0vivo (LLC xenograft) models were deployed to evaluate PPI's efficacy on autophagic flux and the tumour immune microenvironment. The regulatory role of autophagy in macrophage\u2010mediated antigen presentation was scrutinised via ATG3\u2010mediated genetic silencing or overexpression in tumour\u2010macrophage co\u2010culture systems. Concurrently, the capacity of PPI to sensitise NSCLC cells to cisplatin (DDP) and counteract chemoresistance was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PPI activated the AMPK\/p53\/mTOR signalling axis, robustly inducing core autophagic markers (LC3\u2010II and Beclin\u20101) in a dose\u2010dependent manner. Mechanistically, PPI\u2010induced autophagic flux served as a prerequisite for antitumoural M1 macrophage polarisation, characterised by significant upregulation of iNOS and MHC\u2010II in co\u2010cultured THP\u20101 cells. Genetic knockdown of ATG3 effectively abrogated these immunostimulatory profiles, whereas ATG3 overexpression potentiated PPI\u2010driven antigen presentation. Furthermore, PPI administration markedly delayed the onset of DDP resistance sustained by functional autophagic flux. In\u00a0vivo, PPI significantly suppressed tumour burden, accompanied by enhanced CD8+ T\u2010cell infiltration and elevated cytotoxic effector levels (IFN\u2010\u03b3 and Granzyme B).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings establish PPI as a dual autophagic\u2010immune modulator that re\u2010engineers the immunosuppressive microenvironment. By coupling intracellular autophagic stress with macrophage\u2010mediated antigen presentation, PPI reinstates antitumour immunity and abrogates chemoresistance, offering a compelling therapeutic framework for managing recalcitrant NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70149","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:42Z","timestamp":1786665642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphyllin I Orchestrates Autophagy to Reprogram the Tumour Immune Microenvironment and Abrogate Cisplatin Resistance in Non\u2010Small Cell Lung Cancer"],"prefix":"10.1111","volume":"53","author":[{"given":"Zongxu","family":"Liu","sequence":"first","affiliation":[{"name":"Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumin","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-0677","authenticated-orcid":false,"given":"Kunbin","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Urology The 1st Affiliated Hospital of Kunming Medical University  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Wan","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College Yunnan University of Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7801-6993","authenticated-orcid":false,"given":"Xinan","family":"Shi","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine  Kunming China"},{"name":"Yunnan Key Laboratory of Southern Medicinal Utilization Yunnan University of Chinese Medicine  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01740-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-025-00801-x"},{"issue":"2","key":"e_1_2_10_6_1","first-page":"89","article-title":"Autophagy in Major Human Diseases","volume":"26","author":"Klionsky D. 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