[Background] Cancer cachexia is a systemic wasting syndrome, which is characterized by anorexia and the loss of body weight. The central nervous system (CNS) plays a critical role in controlling an appetite. Therefore, this study describes the efficacy of targeting the altered metabolic pathway in the CNS in cachexic mice.
[Methods] Anesthetized 8-week-old male BALB/c nu/nu mice were subcutaneously inoculated with a human gastric cancer cell line, 85As2. Two weeks after inoculation, the brain was collected and quantitative alteration of 96 metabolites was determined using a CETOF-MS system. Xanthine oxidase (XO) activity was also measured by using a fluorescent XO substrate.
[Results] Subcutaneous implantation of 85As2 cells induced progressive tumor growth and significant body weight loss in two weeks, accompanied by gradual decrease of food consumption. Metabolome analysis using the brain showed the decrease of ATP accompanied by the increase of uric acid. Moreover, enzyme activity of XO was increased in the brain of cachexic mice.
[Conclusion] These results suggest that the purine metabolism is activated at the onset of cancer cachexia. Therefore, the effect of febuxostat, a XO inhibitor, is being investigated.