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 pat ients. The Walker 256 tumor has been extensively used as an experiment al model to establish cancer cachexia in rats. This condition is chara cterized by a decrease in food intake and marked degradation of protei ns, lipids and carbohydrate stores leading to cachexia. Walker 256 tum or-bearing rats lose body weight markedly and die in 2 weeks. Our rece nt studies have shown that insulin treatment (5 U/kg body weight per d ay) of Walker 256 tumor-bearing rats partially reverses cancer cachexi a 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 the ir function, (2) inhibition of the metabolism of the tumor causing cel l death and (3) deviation of important metabolites (such as glucose an d glutamine) to insulin-responsive tissues (e.g. skeletal muscle and a dipose tissue), decreasing the availability of metabolites to the tumo r. These three possibilities will be discussed in this review and pers pectives for future research will also be presented.