{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:53:18Z","timestamp":1790931198134,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20240753"],"award-info":[{"award-number":["BK20240753"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Feiwei Heji (FWHJ) is a traditional Chinese medicine formula used for lung cancer with Qi\u2010Yin deficiency. This study investigated the antitumor effect of FWHJ on lung cancer and explored the underlying mechanisms. The major chemical components of FWHJ were identified by HPLC. Lewis lung carcinoma (LLC) tumor\u2010bearing mice received oral FWHJ at different doses. Tumor histopathology was assessed by H&amp;E and TUNEL staining. Expression of MLL4, pyroptosis\u2010related proteins (NLRP3, caspase\u20101, and GSDMD), and inflammatory cytokines (IL\u20101\u03b2 and IFN\u2010\u03b2) was detected by Western blot, immunohistochemistry, and ELISA. Tumor\u2010infiltrating immune cells were evaluated by flow cytometry. An MLL4 overexpression model was established to validate the role of MLL4 in the antitumor effects of FWHJ. HPLC analysis showed that FWHJ primarily contains naringin, chlorogenic acid, amygdalin, and harpagoside. Oral FWHJ significantly inhibited tumor growth, upregulated NLRP3, caspase\u20101, and GSDMD, as well as their cleaved forms, and increased the release of IL\u20101\u03b2 and IFN\u2010\u03b2, indicating the activation of pyroptosis. FWJH also enhanced antitumor immunity, characterized by an increased CD8\n                    <jats:sup>+<\/jats:sup>\n                    \/CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells ratio and elevated proportion of CD28\n                    <jats:sup>+<\/jats:sup>\n                    and IFN\u2010\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the tumor microenvironment. Mechanistically, FWHJ significantly downregulated MLL4 expression, and MLL4 overexpression largely attenuated its antitumor and immune\u2010enhancing effects. These findings suggest that FWHJ suppresses lung cancer progression by downregulating MLL4, activating pyroptosis, and promoting immune cell infiltration, highlighting that MLL4 may serve as a key regulator mediating the antitumor effects of FWHJ.\n                  <\/jats:p>","DOI":"10.1111\/cas.70459","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:59:25Z","timestamp":1785520765000},"page":"2693-2704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Feiwei Heji Enhances Antitumor Immunity by\n                    <scp>MLL4<\/scp>\n                    \u2010Dependent Regulation of Pyroptosis in Lung Cancer"],"prefix":"10.1111","volume":"117","author":[{"given":"Nan","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Guangdong Pharmaceutical University  Guandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5881-6162","authenticated-orcid":false,"given":"Tong","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Integrated Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Xuzhou Hospital of Traditional Chinese Medicine  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-7748","authenticated-orcid":false,"given":"Chufeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology Cancer Hospital of Shandong First Medical University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"794","article-title":"Curcumol Retards Progression of Non\u2010Small Cell Lung Cancer Through the SREBP\u20101\/FASN\/EGFR Pathway","volume":"41","author":"Linglong M.","year":"2025","journal-title":"Journal of Nanjing University of Traditional Chinese Medicine"},{"key":"e_1_2_12_3_1","first-page":"7112","article-title":"Effect and Mechanism of Quercetin on Inhibiting Proliferation of A549 Cells Viainduction of Ferroptosis","volume":"53","author":"Chang L.","year":"2022","journal-title":"Chinese Traditional and Herbal Drugs"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2020.1743911"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15059"},{"key":"e_1_2_12_6_1","first-page":"637","article-title":"Research Progress of Histone 3 Methyltransferase MLL4","volume":"71","author":"Guo H. H.","year":"2019","journal-title":"Sheng Li Xue Bao: [Acta Physiologica Sinica]"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34253-1"},{"key":"e_1_2_12_8_1","first-page":"300","article-title":"Influence of Feiwei Mixture in Chemotherapy Patients With Brain Metastasis of Lung Cancer About Sialic Acid Levels","volume":"35","author":"Zhenmin S.","year":"2016","journal-title":"Journal of Pharmaceutical Research"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26052049"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35849"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.12.013"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154680"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106505"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12101514"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27113637"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15541"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101781"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39938-9"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2025.01.012"},{"key":"e_1_2_12_21_1","first-page":"632","article-title":"Regulatory Mechanisms of Tumor Cell Death and Targeted Interventions","volume":"47","author":"Rong D.","year":"2025","journal-title":"Chinese Journal of Cell Biology"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117371"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2022.1042"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj9141"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70459","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70459","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:05:35Z","timestamp":1790928335000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/cas.70459"],"URL":"https:\/\/doi.org\/10.1111\/cas.70459","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"2026-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}