{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:57:20Z","timestamp":1790661440535,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100029"],"award-info":[{"award-number":["82100029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lung cancer remains a leading cause of cancer\u2010related mortality worldwide, necessitating the development of novel therapeutic strategies. Matrine, a natural alkaloid derived from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Sophora flavescens<\/jats:italic>\n                    <\/jats:styled-content>\n                    , has demonstrated broad antitumor properties, yet its underlying mechanisms, particularly concerning DNA damage response, remain incompletely elucidated. This study integrates network pharmacology, bioinformatics, and experimental validation to uncover a novel dual\u2010targeting mechanism of matrine in lung cancer. Bioinformatics analysis identified CHEK1 as a key potential target. In\u00a0vitro, matrine selectively inhibited proliferation, migration, invasion, and clonogenic survival of A549 and LLC cells, while reducing the G2\/M phase proportion, indicating G2\/M checkpoint impairment. Mechanistically, matrine concurrently downregulated CHEK1, p\u2010PI3K, p\u2010AKT, BCL\u20102, and EMT markers (Vimentin, MMP2, MMP9), and upregulated \u03b3H2AX, E\u2010cadherin, Bax, and Cleaved Caspase\u20103. Crucially, siRNA experiments revealed that PI3K knockdown induced apoptosis without affecting CHEK1\/\u03b3H2AX, whereas CHEK1 silencing promoted apoptosis independently of PI3K\/AKT, demonstrating complementary. In\u00a0vivo, matrine significantly inhibited LLC tumor growth in a xenograft model, suppressed proliferation (Ki67), and modulated the CHEK1\u2010PI3K\/AKT axis, corroborated by IHC and Western blotting. Importantly, matrine exhibited no significant systemic toxicity. Our findings unveil that matrine exerts potent antitumor effects by simultaneously inhibiting CHEK1\u2010mediated DNA repair and PI3K\/AKT survival signaling, presenting a novel dual\u2010targeting approach for lung cancer treatment.\n                  <\/jats:p>","DOI":"10.1111\/1759-7714.70393","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:34:57Z","timestamp":1790123697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Matrine Suppresses Lung Cancer Progression via Dual Inhibition of\n                    <scp>CHEK1<\/scp>\n                    \u2010Mediated\n                    <scp>DNA<\/scp>\n                    Damage Repair and\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Survival Signaling"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9503-1523","authenticated-orcid":false,"given":"Jianghao","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Center for Oncology Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwu","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeshan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changshuai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqing","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzhe","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Center for Oncology Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0762-5946","authenticated-orcid":false,"given":"Yun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Center for Oncology Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu China"},{"name":"Zhejiang Key Laboratory of Precision Diagnosis and Treatment for Lung Cancer  Yiwu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Center for Oncology Medical, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine Zhejiang University  Yiwu 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