Reversion of Walker 256 tumor cachexia by insulin treatment: possible mechanisms involved and perspectives for future research

Cancer cachexia is assumed to be the major cause of death of tumor patients. The Walker 256 tumor has been extensively used as an experimental model to establish cancer cachexia in rats. This condition is characterized by a decrease in food intake and marked degradation of proteins, lipids and carbohydrate stores leading to cachexia. Walker 256 tumor-bearing rats lose body weight markedly and die in 2 weeks. Our recent studies have shown that insulin treatment (5 U/kg body weight per day) of Walker 256 tumor-bearing rats partially reverses cancer cachexia and causes a marked reduction (about 90%) of the tumor weight. This intriguing observation led us to consider three possible explanations for the beneficial effects of insulin treatment in tumor-bearing rats: (1) stimulation of lymphocyte and macrophage metabolism and so of their function, (2) inhibition of the metabolism of the tumor causing cell death and (3) deviation of important metabolites (such as glucose and glutamine) to insulin-responsive tissues (e.g. skeletal muscle and adipose tissue), decreasing the availability of metabolites to the tumor. These three possibilities will be discussed in this review and perspectives for future research will also be presented.