{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:51:22Z","timestamp":1790387482260,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T00:00:00Z","timestamp":1436227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"crossref","award":["IG9153"],"award-info":[{"award-number":["IG9153"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Muscle wasting, a prominent feature of cancer cachexia, is mainly caused by sustained protein hypercatabolism. The enhanced muscle protein degradation rates rely on the activity of different proteolytic systems, although the Adenosine triphosphate (ATP)\u2010ubiquitin\u2010proteasome\u2010dependent pathway and autophagy have been shown to play a pivotal role. Bortezomib is a potent reversible and selective proteasome and NF\u2010\u03baB inhibitor approved for the clinical use, which has been shown to be effective in preventing muscle wasting in different catabolic conditions. The aim of the present study has been to investigate whether pharmacological inhibition of proteasome by bortezomib may prevent skeletal muscle wasting in experimental cancer cachexia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cancer cachexia was induced in rats by intraperitoneal injection of Yoshida AH\u2010130 ascites hepatoma cells and in mice by subcutaneous inoculation of C26 carcinoma cells. Animals were then further randomized to receive bortezomib. The AH\u2010130 hosts were weighted and sacrificed under anaesthesia, on Days 3, 4, 5, and 7 after tumour inoculation, while C26\u2010bearing mice were weighted and sacrificed under anaesthesia 12\u2009days after tumour transplantation. NF\u2010\u03baB and proteasome activation, MuRF1 and atrogin\u20101 mRNA expression and beclin\u20101 protein levels were evaluated in the gastrocnemius of controls and AH\u2010130 hosts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bortezomib administration in the AH\u2010130 hosts, although able to reduce proteasome and NF\u2010\u03baB DNA\u2010binding activity in the skeletal muscle on Day 7 after tumour transplantation, did not prevent body weight loss and muscle wasting. In addition, bortezomib exerted a transient toxicity, as evidenced by the reduced food intake and by the increase in NF\u2010\u03baB DNA\u2010binding activity in the AH\u2010130 hosts 3\u2009days after tumour transplantation. Beclin\u20101 protein levels were increased by bortezomib treatment in Day 3 controls but were unchanged on both Days 3 and 7 in the AH\u2010130 hosts, suggesting that an early compensatory induction of autophagy may exist in healthy but not in tumour\u2010bearing animals. Regarding C26\u2010bearing mice, bortezomib did not prevent as well body and muscle weight loss 12\u2009days after tumour implantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results obtained suggest that proteasome inhibition by bortezomib is not able to prevent muscle wasting in experimental cancer cachexia. Further studies are needed to address the issue whether a different dosage of bortezomib alone or in combination with other drugs modulating different molecular pathways may effectively prevent muscle wasting during cancer cachexia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12050","type":"journal-article","created":{"date-parts":[[2015,7,8]],"date-time":"2015-07-08T01:11:08Z","timestamp":1436317868000},"page":"345-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Effect of the specific proteasome inhibitor bortezomib on cancer\u2010related muscle wasting"],"prefix":"10.1002","volume":"7","author":[{"given":"Fabio","family":"Penna","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bonetto","sequence":"additional","affiliation":[{"name":"Department of 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