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Clinical treatment of cancer cachexia is mainly based on nutritional therapy and physical exercise; medication only improves appetite but does not reverse the symptoms of skeletal muscle wasting. In this work, we systematically studied the underlying molecular mechanisms by which cucurbitacin IIb (CuIIb) ameliorates muscle wasting in cancer cachexia both in vitro and in vivo. CuIIb significantly ameliorated the chief features of cancer cachexia in vivo, alleviating weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reductions. In vitro, CuIIb (10 and 20\u2009\u03bcM) dose\u2010dependently attenuated conditioned medium (CM)\u2010induced C2C12 myotube atrophy. Collectively, our findings demonstrated that CuIIb prevented the upregulation of the E3 ubiquitin ligase muscle atrophy Fbox protein (MAFbx), myosin heavy chain (MyHC), and myogenin (MyoG) and impacted protein synthesis and degradation. In addition, CuIIb decreased the phosphorylation of Tyr705 in STAT3 by regulating the IL\u20106\/STAT3\/FoxO pathway to reduce skeletal muscle atrophy in cancer cachexia.<\/jats:p>","DOI":"10.1002\/ptr.7811","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T11:29:34Z","timestamp":1681903774000},"page":"3380-3393","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cucurbitacin <scp>IIb<\/scp> attenuates cancer cachexia induced skeletal muscle atrophy by regulating the <scp>IL<\/scp>\u20106\/<scp>STAT3<\/scp>\/<scp>FoxO<\/scp> signaling pathway"],"prefix":"10.1002","volume":"37","author":[{"given":"Yaxian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xipeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanjun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-8496","authenticated-orcid":false,"given":"Cheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.184507"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14092107"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v7.i4.17"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140403"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.12.123"},{"key":"e_1_2_10_7_1","first-page":"1704","volume-title":"Identification of ubiquitin ligases required for skeletal muscle atrophy. 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