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Article

Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma

  • Authors:
    • Xing-Yu Lin
    • Si-Zeng Chen
  • View Affiliations / Copyright

    Affiliations: The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
  • Pages: 1601-1610
    |
    Published online on: January 20, 2017
       https://doi.org/10.3892/or.2017.5396
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Abstract

Cancer-related cachexia involves increased protein breakdown through various proteolytic pathways, including the ubiquitin-proteasome pathway (UPP). We hypothesized that a calcium- and calpain-dependent pathway might play a crucial role during the proteolytic procedure, and that pathway interventions would ameliorate cancer cachexia in vivo. After being inoculated with CT26 adenocarcinoma cell culture subcutaneously, BALB/c mice developed cachexia in 12 days. They were then administered with different types of calpain inhibitors individually or in combination for 7 consecutive days. Eighteen healthy mice were also assessed as a control group. Changes in body weight, gastrocnemius muscle mass, tumor volume, food intake, survival time, and serum nutritional markers were monitored. Also measured were the levels of calpains, E3 ubiquitin ligases, and apoptosis-associated markers in gastrocnemius muscle. Our study showed that the intraperitoneal administration of calpain inhibitors significantly improved tumor-free body weight and gastrocnemius muscle mass in all treatment groups. Treatment with calpain inhibitors also ameliorated cachexia-associated negative effects in metabolic profiles and increased survival time in most of the tumor-bearing mice compared with the cachexia controls. Furthermore, calpain inhibitors reduced the calpain activity and the expression of MuRF-1 and atrogin-1 in all treatment groups, while increasing the level of cleaved caspase-3 and BAX and lowering the level of BCL-2 in some groups. These results justify further evaluation of calpain inhibitors both alone and in combination with other candidate agents as a potential new therapeutic strategy for treating cancer cachexia.
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Copy and paste a formatted citation
Spandidos Publications style
Lin X and Chen S: Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma. Oncol Rep 37: 1601-1610, 2017.
APA
Lin, X., & Chen, S. (2017). Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma. Oncology Reports, 37, 1601-1610. https://doi.org/10.3892/or.2017.5396
MLA
Lin, X., Chen, S."Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma". Oncology Reports 37.3 (2017): 1601-1610.
Chicago
Lin, X., Chen, S."Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma". Oncology Reports 37, no. 3 (2017): 1601-1610. https://doi.org/10.3892/or.2017.5396
Copy and paste a formatted citation
x
Spandidos Publications style
Lin X and Chen S: Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma. Oncol Rep 37: 1601-1610, 2017.
APA
Lin, X., & Chen, S. (2017). Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma. Oncology Reports, 37, 1601-1610. https://doi.org/10.3892/or.2017.5396
MLA
Lin, X., Chen, S."Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma". Oncology Reports 37.3 (2017): 1601-1610.
Chicago
Lin, X., Chen, S."Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma". Oncology Reports 37, no. 3 (2017): 1601-1610. https://doi.org/10.3892/or.2017.5396
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