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Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model

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Tumor Biology

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.

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Acknowledgments

This study was supported by a research grant (no. JS06045) from the Professor Academic Development Fund of Fujian Medical University.

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  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Fujian Medical University, No. 20 Chating Zhong Road, Fuzhou, Fujian, 350005, People’s Republic of China

    Si-Zeng Chen & Jian-Dong Xiao

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Correspondence to Si-Zeng Chen.

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Chen, SZ., Xiao, JD. Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model. Tumor Biol. 35, 323–332 (2014). https://doi.org/10.1007/s13277-013-1043-1

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