{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:57:44Z","timestamp":1793159864741,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Ruxolitinib (Rux), an oral Janus tyrosine Kinase (JAK) tyrosine kinase inhibitor, has demonstrated anti-inflammatory properties and the ability to mitigate denervation-induced skeletal muscle atrophy. Here, we checked the potential efficacy of Rux on cancer cachexia and tried to clarified its mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The in vitro cell models of C26 or LLC CM-induced C2C12 myotubes were used to check the influence of Rux on myotube atrophy. C26 tumour-bearing mice (male BALB\/c mice) were applied as the animal model to examine the effects of Rux in attenuating cachexia symptoms. Western blot analysis was utilized to investigate the potential mechanisms of Rux.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Rux significantly attenuated C2C12 myotube atrophy in vitro. Rux suppressed the interleukin-6 secretion by inhibiting STAT3 activation in tumour cells and macrophages. The administration of Rux prevented body weight loss and muscle wasting in C26 tumour-bearing mice without affecting tumour growth. At the end of the experiment, mice in the Rux treatment group exhibited a 6.7% increase in body weight compared to the C26 model group. Furthermore, Rux enhanced in gastrocnemius myofibres cross-sectional area and grip strength.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Rux ameliorates cancer cachexia muscle atrophy by inhibiting STAT3\/Atrogin-1 signaling. Rux may represent a promising therapeutic candidate for the treatment of cancer cachexia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf073","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T11:37:08Z","timestamp":1754480228000},"page":"1715-1725","source":"Crossref","is-referenced-by-count":6,"title":["Ruxolitinib alleviated muscle atrophy in cancer cachexia by inhibiting IL-6\/JAK\/STAT3 signaling pathway in mice"],"prefix":"10.1093","volume":"77","author":[{"given":"Cong","family":"Li","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Gu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, East China Normal University , Shanghai 200062 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine , Shanghai 201003 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-4190","authenticated-orcid":false,"given":"Xiongwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"2025120200421751200_ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejphar.2014.09.025","article-title":"Ghrelin relieves cancer cachexia associated with the development of lung adenocarcinoma in mice","volume":"743","author":"Tsubouchi","year":"2014","journal-title":"Eur J Pharmacol"},{"key":"2025120200421751200_ref2","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41571-023-00734-5","article-title":"Cancer-associated cachexia - understanding the tumour macroenvironment and microenvironment to improve management","volume":"20","author":"Argil\u00e9s","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"2025120200421751200_ref3","doi-asserted-by":"publisher","first-page":"791060","DOI":"10.1155\/2015\/791060","article-title":"Cancer as a proinflammatory environment: metastasis and cachexia","volume":"2015","author":"In\u00e1cio Pinto","year":"2015","journal-title":"Mediat Inflamm"},{"key":"2025120200421751200_ref4","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1097\/01.mco.0000165004.93707.88","article-title":"Systemic inflammation, cachexia and prognosis in patients with cancer","volume":"8","author":"Deans","year":"2005","journal-title":"Curr Opin Clin Nutr Metabolic Care"},{"key":"2025120200421751200_ref5","doi-asserted-by":"publisher","first-page":"e0161125","DOI":"10.1371\/journal.pone.0161125","article-title":"The relationship between sarcopenia and systemic inflammatory response for cancer cachexia in small cell lung cancer","volume":"11","author":"Kim","year":"2016","journal-title":"PLoS One"},{"key":"2025120200421751200_ref6","doi-asserted-by":"publisher","DOI":"10.3390\/cells12222598","article-title":"Unravelling the role of cancer cell-derived extracellular vesicles in muscle atrophy, lipolysis, and cancer-associated cachexia","volume":"12:2598","author":"Marzan","year":"2023","journal-title":"Cells"},{"key":"2025120200421751200_ref7","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13045-023-01454-0","article-title":"Cancer cachexia: molecular mechanisms and treatment strategies","volume":"16","author":"Setiawan","year":"2023","journal-title":"J Hematol Oncol"},{"key":"2025120200421751200_ref8","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41577-021-00624-w","article-title":"The interplay of immunology and cachexia in infection and cancer","volume":"22","author":"Baazim","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"2025120200421751200_ref9","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.ccell.2024.03.009","article-title":"The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia","volume":"42","author":"Liu","year":"2024","journal-title":"Cancer Cell"},{"key":"2025120200421751200_ref10","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1152\/japplphysiol.01026.2004","article-title":"IL-6-induced skeletal muscle atrophy","volume":"98","author":"Haddad","year":"2005","journal-title":"J Appl Physiol"},{"key":"2025120200421751200_ref11","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1172\/jci118398","article-title":"Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice","volume":"97","author":"Tsujinaka","year":"1996","journal-title":"J Clin Invest"},{"key":"2025120200421751200_ref12","doi-asserted-by":"publisher","first-page":"E410","DOI":"10.1152\/ajpendo.00039.2012","article-title":"JAK\/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia","volume":"303","author":"Bonetto","year":"2012","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2025120200421751200_ref13","doi-asserted-by":"publisher","first-page":"1031906","DOI":"10.3389\/fphar.2022.1031906","article-title":"C188-9, a specific inhibitor of STAT3 signaling, prevents thermal burn-induced skeletal muscle wasting in mice","volume":"13","author":"Ono","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025120200421751200_ref14","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1002\/jcsm.12867","article-title":"Sepsis induces interleukin 6, gp130\/JAK2\/STAT3, and muscle wasting","volume":"13","author":"Zanders","year":"2022","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"2025120200421751200_ref15","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.043166","article-title":"HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia","volume":"13","author":"Huot","year":"2020","journal-title":"Dis Model Mech"},{"key":"2025120200421751200_ref16","doi-asserted-by":"publisher","first-page":"819","DOI":"10.4149\/bll_2019_136","article-title":"IL-6 mediated JAK\/STAT3 signaling pathway in cancer patients with cachexia","volume":"120","author":"Eskiler","year":"2019","journal-title":"Bratislavske lekarske listy"},{"key":"2025120200421751200_ref17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218261","article-title":"Targeting the JAK2\/STAT3 pathway-can we compare it to the two faces of the god Janus?","volume":"21","author":"Ja\u015bkiewicz","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2025120200421751200_ref18","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"2025120200421751200_ref19","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s13045-023-01471-z","article-title":"Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety","volume":"16","author":"Verstovsek","year":"2023","journal-title":"J Hematol Oncol"},{"key":"2025120200421751200_ref20","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/978-3-319-91439-8_6","article-title":"Ruxolitinib","volume":"212","author":"Ajayi","year":"2018","journal-title":"Recent results in cancer research Fortschritte der Krebsforschung Progres dans les recherches sur le cancer"},{"key":"2025120200421751200_ref21","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.2217\/fon.11.81","article-title":"Ruxolitinib: a new JAK1\/2 inhibitor that offers promising options for treatment of myelofibrosis","volume":"7","author":"Ostojic","year":"2011","journal-title":"Future Oncol (London, England)"},{"key":"2025120200421751200_ref22","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14051001","article-title":"A comprehensive overview of globally approved JAK inhibitors","volume":"14","author":"Shawky","year":"2022","journal-title":"Pharmaceutics"},{"key":"2025120200421751200_ref23","doi-asserted-by":"publisher","first-page":"650295","DOI":"10.3389\/fphar.2021.650295","article-title":"Ruxolitinib, a JAK1\/2 inhibitor, ameliorates cytokine storm in experimental models of hyperinflammation syndrome","volume":"12","author":"Huarte","year":"2021","journal-title":"Front Pharmacol"},{"key":"2025120200421751200_ref24","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3164\/jcbn.19-10","article-title":"Dietary intake of probiotic kimchi ameliorated IL-6-driven cancer cachexia","volume":"65","author":"An","year":"2019","journal-title":"J Clin Biochem Nutr"},{"key":"2025120200421751200_ref25","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1002\/jcsm.12710","article-title":"Carnosol and its analogues attenuate muscle atrophy and fat lipolysis induced by cancer cachexia","volume":"12","author":"Lu","year":"2021","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"2025120200421751200_ref26","doi-asserted-by":"publisher","first-page":"116846","DOI":"10.1016\/j.taap.2024.116846","article-title":"Paeoniflorin alleviated muscle atrophy in cancer cachexia through inhibiting TLR4\/NF-\u03baB signaling and activating AKT\/mTOR signaling","volume":"484","author":"Zhu","year":"2024","journal-title":"Toxicol Appl Pharmacol"},{"key":"2025120200421751200_ref27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.scr.2018.07.004","article-title":"Shisa2 regulates the fusion of muscle progenitors","volume":"31","author":"Liu","year":"2018","journal-title":"Stem Cell Res"},{"key":"2025120200421751200_ref28","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ejphar.2017.05.036","article-title":"Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in colon 26 tumor-bearing mice","volume":"811","author":"Yoshimura","year":"2017","journal-title":"Eur J Pharmacol"},{"key":"2025120200421751200_ref29","doi-asserted-by":"publisher","first-page":"714943","DOI":"10.3389\/fimmu.2021.714943","article-title":"Janus kinase inhibition ameliorates ischemic stroke injury and neuroinflammation through reducing NLRP3 inflammasome activation via JAK2\/STAT3 pathway inhibition","volume":"12","author":"Zhu","year":"2021","journal-title":"Front Immunol"},{"key":"2025120200421751200_ref30","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1186\/s40064-016-2197-2","article-title":"Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6","volume":"5","author":"Beliz\u00e1rio","year":"2016","journal-title":"SpringerPlus"},{"key":"2025120200421751200_ref31","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123527","article-title":"Decreased miR-497-5p suppresses IL-6 induced atrophy in muscle cells","volume":"10","author":"Freire","year":"2021","journal-title":"Cells"},{"key":"2025120200421751200_ref32","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cmet.2012.06.011","article-title":"Cancer cachexia: mediators, signaling, and metabolic pathways","volume":"16","author":"Fearon","year":"2012","journal-title":"Cell Metab"},{"key":"2025120200421751200_ref33","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1111\/jcmm.14930","article-title":"LPS-induced inflammation desensitizes hepatocytes to Fas-induced apoptosis through Stat3 activation-the effect can be reversed by ruxolitinib","volume":"24","author":"Markotic","year":"2020","journal-title":"J Cell Mol Med"},{"key":"2025120200421751200_ref34","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.21037\/atm-20-7269","article-title":"Inhibition of IL-6\/JAK\/STAT3 pathway rescues denervation-induced skeletal muscle atrophy","volume":"8","author":"Huang","year":"2020","journal-title":"Ann Transl Med"},{"key":"2025120200421751200_ref35","doi-asserted-by":"publisher","first-page":"6587","DOI":"10.1113\/jp284808","article-title":"Inflammation o'clock: interactions of circadian rhythms with inflammation-induced skeletal muscle atrophy","volume":"602","author":"Morena","year":"2023","journal-title":"J Physiol"},{"key":"2025120200421751200_ref36","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: understanding the molecular basis","volume":"14","author":"Argil\u00e9s","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"2025120200421751200_ref37","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1358\/dot.2022.58.3.3381585","article-title":"Anamorelin for cancer cachexia","volume":"58","author":"Nishie","year":"2022","journal-title":"Drugs of Today (Barcelona, Spain: 1998)"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/77\/12\/1715\/64096238\/rgaf073.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/77\/12\/1715\/64096238\/rgaf073.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:42:24Z","timestamp":1764654144000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/77\/12\/1715\/8238764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,8,20]]},"published-print":{"date-parts":[[2025,11,28]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgaf073","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,8,20]]}}}