{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:00:41Z","timestamp":1785416441887,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia","award":["SKL-HIDCA-2023-JY6"],"award-info":[{"award-number":["SKL-HIDCA-2023-JY6"]}]},{"DOI":"10.13039\/501100004880","name":"Xinjiang Medical University","doi-asserted-by":"crossref","award":["0103010211"],"award-info":[{"award-number":["0103010211"]}],"id":[{"id":"10.13039\/501100004880","id-type":"DOI","asserted-by":"crossref"}]},{"award":["0103010211"],"award-info":[{"award-number":["0103010211"]}],"id":[{"id":"https:\/\/ror.org\/01p455v08","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460714"],"award-info":[{"award-number":["82460714"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82460714"],"award-info":[{"award-number":["82460714"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Xinjiang Uygur Autonomous Region Tianchi Talent Introduction Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis, largely due to therapeutic resistance and the limited availability of effective targeted therapies. Aloperine (ALO), a natural alkaloid derived from Sophora alopecuroides L., exhibits anti-cancer properties in various tumor types; however, its therapeutic potential and underlying mechanism in ESCC remain unclear. Here, we report that ALO inhibited ESCC cell proliferation and colony formation in a dose- and time-dependent manner and induced caspase-dependent apoptosis, accompanied by loss of mitochondrial membrane potential and PARP1 cleavage. Mechanistically, ALO significantly suppressed inflammatory pathways, with IL-6 identified as a critical downregulated target. ALO inhibited IL-6 production by targeting the AP-1 transcription factor complex, as evidenced by reduced cFOS expression and suppressed cJUN phosphorylation. Consequently, ALO inhibited downstream IL-6\/JAK-STAT3 signaling. Functionally, exogenous IL-6 rescued ALO-induced loss of cell viability. Notably, the combination of ALO with cisplatin exerted synergistic antitumor effects. In a syngeneic mice model, the combination therapy significantly reduced tumor growth and Ki67 expression while inducing apoptosis, as shown by increased TUNEL staining and cleaved caspase-3 expression, and further suppressing the IL-6\/STAT3 axis compared with either monotherapy. Together, these findings demonstrate that ALO exerts potent anti-ESCC activity by targeting the AP-1\/IL-6\/STAT3 signaling axis. The synergistic efficacy of ALO with cisplatin highlights its potential as a promising therapeutic agent to overcome chemoresistance and improve outcomes in ESCC patients.<\/jats:p>","DOI":"10.3390\/biom16060791","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:36:56Z","timestamp":1779892616000},"page":"791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aloperine Suppresses the Tumorigenicity of Esophageal Squamous Cell Carcinoma by Targeting the AP-1\/IL-6\/STAT3 Signaling Axis"],"prefix":"10.3390","volume":"16","author":[{"given":"Ba-Fang","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Nan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Die","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchao","family":"Guan","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ping","family":"Liang","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Women\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Hao","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1990-4857","authenticated-orcid":false,"given":"Yasen","family":"Maimaitiyiming","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China"},{"name":"Institute of Basic Medical Sciences, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8988","DOI":"10.1038\/s41467-024-53164-x","article-title":"The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma","volume":"15","author":"Jiang","year":"2024","journal-title":"Nat. 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