Higher skeletal muscle protein synthesis and lower breakdown after chemotherapy in cachectic mice
American Journal of Physiology. Regulatory Integrative and Comparative Physiology
Higher skeletal muscle protein synthesis and lower breakdown after chemotherapy in cachectic mice. Am J Physiol Regulatory Integrative Comp Physiol 281: R133-R139, 2001.-The influence of cancer cachexia and chemotherapy and subsequent recovery of skeletal muscle protein mass and turnover was investigated in mice. Cancer cachexia was induced using colon 26 adenocarcinoma, which is characteristic of the human condition, and can be cured with 100% efficacy using an experimental nitrosourea,
... stine (C 6 H 12 CIN 3 O 4 S). Reduced food intake was not a factor in these studies. Three days after cachexia began, healthy and tumor-bearing mice were given a single intraperitoneal injection of cystemustine (20 mg/kg). Skeletal muscle mass in tumor-bearing mice was 41% lower (P Ͻ 0.05) than in healthy mice 2 wk after cachexia began. Skeletal muscle wasting was mediated initially by decreased protein synthesis (Ϫ38%; P Ͻ 0.05) and increased degradation (ϩ131%; P Ͻ 0.05); later wasting resulted solely from decreased synthesis (ϳϪ54 to Ϫ69%; P Ͻ 0.05). Acute cytotoxicity of chemotherapy did not appear to have an important effect on skeletal muscle protein metabolism in either healthy or tumor-bearing mice. Recovery began 2 days after treatment; skeletal muscle mass was only 11% lower than in healthy mice 11 days after chemotherapy. Recovery of skeletal muscle mass was affected initially by decreased protein degradation (Ϫ80%; P Ͻ 0.05) and later by increased protein synthesis (ϩ46 to ϩ73%; P Ͻ 0.05) in cured compared with healthy mice. This study showed that skeletal muscle wasted from cancer cachexia and after chemotherapeutic treatment is able to generate a strong anabolic response by making powerful changes to protein synthesis and degradation.