Tayek J A, Blackburn G L, Bistrian B R
Laboratory of Nutrition/Infection, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Cancer Res. 1988 Mar 15;48(6):1554-8.
The rate of protein synthesis in vivo was assessed in tumor tissue, skeletal muscle, liver, and the whole body of rats bearing either the Yoshida sarcoma or Novikoff hepatoma after 18 days of tumor growth and compared to tumor-free controls. Changes in size of the whole animal and tumor (i.e., growth) were measured, and fractional rates of growth, synthesis, and degradation were estimated. Muscle protein synthesis and whole-body growth were significantly reduced in both groups of tumor-bearing rats after 18 days of tumor growth. In addition to reductions in muscle protein synthesis, whole-body protein synthesis was significantly reduced in the Yoshida tumor-bearing group (587 +/- 36 versus 401 +/- 40 mg/h; mean +/- SEM; control versus Yoshida group, respectively, P less than 0.01). Tumor protein synthesis was not statistically different between the Yoshida tumor (76 +/- 21 mg/h) and the Novikoff tumor (50 +/- 8) after 18 days of growth despite the fact that the Yoshida tumors were significantly larger (33.9 +/- 4.2 g versus 11.9 +/- 1.2 g; P less than 0.01). The fractional synthesis rate (Ks) was, in fact, significantly slower in the Yoshida versus the Novikoff tumor (36.8 +/- 7.6 versus 55.1 +/- 4.8%/day). Tumor growth (Kg) followed first order growth rates for both tumor types (r = 0.945, 0.869; Kg = 17.2 +/- 1.6, 15.5 +/- 1.9%/day; Yoshida and Novikoff, respectively). The fractional degradation rate of tumor protein (Kd) was determined as the difference between the two first order rate constants Ks and Kg. The tumor protein degradation rate was significantly reduced in the Yoshida tumors compared to the Novikoff tumors (19.6 +/- 8.2% versus 39.6 +/- 4.2%/day, respectively). The greater size in the Yoshida sarcoma can be attributed to reduction in fractional protein degradation rather than change in synthesis rates, which supports the theory that some tumors can regulate their growth by alteration in tumor protein degradation rates (J. A. Tayek et al., Cancer Res., 46:5649-5654, 1986).
在肿瘤生长18天后，对携带吉田肉瘤或诺维科夫肝癌的大鼠的肿瘤组织、骨骼肌、肝脏及全身的体内蛋白质合成速率进行评估，并与无肿瘤对照进行比较。测量了整个动物和肿瘤的大小变化（即生长情况），并估算了生长、合成及降解的分数速率。在肿瘤生长18天后，两组荷瘤大鼠的肌肉蛋白质合成和全身生长均显著降低。除了肌肉蛋白质合成减少外，吉田荷瘤组的全身蛋白质合成也显著降低（分别为587±36与401±40mg/h；均值±标准误；对照组与吉田组，P＜0.01）。尽管吉田肿瘤明显更大（33.9±4.2g对11.9±1.2g；P＜0.01），但生长18天后，吉田肿瘤（76±21mg/h）和诺维科夫肿瘤（50±8）的肿瘤蛋白质合成在统计学上并无差异。实际上，吉田肿瘤的分数合成速率（Ks）显著慢于诺维科夫肿瘤（36.8±7.6对55.1±4.8%/天）。两种肿瘤类型的肿瘤生长（Kg）均遵循一级生长速率（r = 0.945，0.869；Kg = 17.2±1.6，15.5±1.9%/天；分别为吉田肿瘤和诺维科夫肿瘤）。肿瘤蛋白质的分数降解速率（Kd）通过两个一级速率常数Ks和Kg的差值来确定。与诺维科夫肿瘤相比，吉田肿瘤的肿瘤蛋白质降解速率显著降低（分别为19.6±8.2%对39.6±4.2%/天）。吉田肉瘤更大的体积可归因于蛋白质分数降解的降低而非合成速率的改变，这支持了某些肿瘤可通过改变肿瘤蛋白质降解速率来调节其生长的理论（J.A. 塔耶克等人，《癌症研究》，46:5649 - 5654，1986）。
