title: Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model.
abstract: Rosiglitazone (RGZ) and imidapril improve cancer cachexia via different mechanisms. Therefore, we hypothesized that combination therapy of RGZ+imidapril would further attenuate cancer cachexia in vivo. After injection with colon-26 adenocarcinoma for 9 days, BALB/c mice were randomly divided into the following four treatment groups for 7 days (n = 8 per group): (1) placebo, (2) RGZ, (3) imidapril, and (4) RGZ+imidapril. Eight healthy control animals were also assessed. Body weight, tumor volume, gastrocnemius muscle and epididymal adipose mass, serum metabolic markers and cytokines, and the expression of nuclear factor-κB and two E3 ubiquitin ligases, atrogin-1 and MuRF-1, were measured. From days 14 to 16, all treatments significantly reduced tumor volume (P < 0.05). From days 10 to 16, improvements in the tumor-free body weight were observed in the RGZ and RGZ+imidapril groups. In addition, significant improvements in both gastrocnemius muscle and epididymal adipose mass were observed in all treatment groups (all, P < 0.05). Furthermore, all treatments significantly increased tumor necrosis factor alpha levels as compared to those observed in the healthy control animals (P < 0.001). Insulin levels significantly increased in the placebo group as compared to those in the healthy control group (P < 0.05), which were reduced in all the treatment groups (P < 0.05). Finally, whereas all treatments significantly reduced atrogin-1 levels as compared to the placebo group (all, P < 0.05), significant reductions in MuRF-1 levels were only observed in the RGZ and RGZ+imidapril groups (both, P < 0.05). Thus, all three treatments reduce tumor growth and alleviate cancer cachexia; however, synergistic effects of RGZ+imidapril combination therapy were not observed.
authors: Si-Zeng
authors: SZ
authors: Chen
authors: Jian-Dong
authors: JD
authors: Xiao
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation / Q000187:drug effects; D048289:Imidazolidines / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D009133:Muscular Atrophy / Q000188:drug therapy; D009369:Neoplasms / Q000150:complications* / Q000473:pathology; D009929:Organ Size; D000077154:Rosiglitazone; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D000070584:Tripartite Motif Proteins; D047368:Tumor Burden; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D048289:Imidazolidines; D018836:Inflammation Mediators; D007328:Insulin; D009124:Muscle Proteins; D045162:Thiazolidinediones; D000070584:Tripartite Motif Proteins; D000077154:Rosiglitazone; C065166:imidapril; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
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