Acylated and unacylated ghrelin inhibit atrophy in myotubes co-cultured with colon carcinoma cells
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Xianliang Zeng1, Sizeng Chen1, Yang Yang1 and Zhao Ke1
1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, China
Sizeng Chen, email: [email protected]
Keywords: cancer cachexia, ghrelin, co-culture, calpain, myotube
Received: March 24, 2017 Accepted: July 30, 2017 Published: August 24, 2017
Cancer cachexia is a result of increased protein degradation and decreased protein synthesis. The multifunctional circulating hormone ghrelin promotes synthesis and inhibits degradation of muscle protein, but its mechanism of action is not fully understood. Here, we investigated whether co-culturing C2C12 myotubes with CT26 colon carcinoma cells induces myotube atrophy, and whether acylated ghrelin (AG) and unacylated ghrelin (UnAG) had anti-atrophic effects. We found that co-culture induced myotube atrophy and increased tumor necrosis factor-alpha (TNF-α) and myostatin concentrations in the culture medium. Moreover, co-culture down-regulated myogenin and MyoD expression, inhibited the Akt signaling, up-regulated ubiquitin E3 ligase expression, and activated the calpain system and autophagy in myotubes. Both AG and UnAG inhibited these changes. Our study describes a novel in vitro model that can be employed to investigate cancer cachexia, and our findings suggest a possible use for AG and UnAG in treating cancer cachexia.
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