Protein Metabolism in Cachectic Tumor-Bearing Rats: Effect of Tumor Excision

Abstract

The effect of tumor resection on protein metabolism in cancer-bearing subjects is poorly documented. We explored changes in nitrogen (N) and protein metabolism after excision of tumors both at the whole body level (N balance) and at the tissue level, including skeletal muscle, small intestine, and liver. Sixteen male Sprague–Dawley rats (∼375 g) bearing subcutaneous Morris hepatoma 7777 for 6 weeks were either operated for tumor excision and studied for 10 days postoperatively (n= 10) or sacrificed on the day of surgery as tumor-bearing controls; operated and unoperated tumor-bearing rats were compared with healthy rats (n= 16). Tumors, which grew to a mass of 74 ± 7 g (mean ± SEM), induced significant loss of body mass (−27 ± 13 g) and protein depletion in epitrochlearis muscle (EPI) (−38%) and small intestine (−42%) vs healthy rats. Tumor significantly decreased muscle protein synthesis vs healthy rats (7.14 ± 0.5 vs 10.7 ± 0.5 nmol phenylalanine (Phe)/EPI/3 hr), net degradation (21.7 ± 2.9 vs 30.6 ± 2.5 nmol Phe/EPI/3 hr) and degradation (28.8 ± 2.7 vs 41.4 ± 2.5 nmol Phe/EPI/3 hr). In 50% of operated rats, tumor removal was followed immediately by increased food intake, body weight, and N balance; in other rats, this was delayed by 2–4 days. By 6 days postoperative, all rats were gaining weight and had normal food intake; wasting was abolished in small intestine, but not in skeletal muscle (protein mass −43% vs healthy rats,P< 0.05). Postoperative rats maintained lower muscle protein degradation (28.2 ± 2.0 vs 41.4 ± 2.5 nmol Phe/EPI/3 hr,P< 0.05) than healthy rats; protein synthesis was no longer reduced. In skeletal muscle, protein synthesis and protein deposition were related to levels of postoperative food intake (r= 0.91 and 0.98, respectively;P< 0.05). Following tumor excision, reversal of cancer cachexia appeared to be highly dependent on the level of postoperative food intake.