Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics.
Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics.
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从蛋白质代谢和细胞周期动力学方面评价肿瘤坏死因子的抗肿瘤作用。
DOI：
10.1152/ajpcell.1993.265.2.c365
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Istfan,NW
中科院分区：
文献类型：
--
作者：
Wan,JM;Fogt,F;Bistrian,BR;Istfan,NW
为了确定蛋白质分解在调节肿瘤生长中的意义，更好地了解肿瘤坏死因子在体内的抗肿瘤机制，我们测量了持续静脉输注人重组肿瘤坏死因子- α (rHuTNF) 6小时对患Walker-256癌肉瘤大鼠肿瘤蛋白代谢和细胞周期动力学的影响。用[14C]亮氨酸输注研究蛋白质代谢；利用5-溴-2'-脱氧尿苷（BrdUrd）脉冲标记和流式细胞术双变量BrdUrd/DNA分析，在体内估计肿瘤细胞周期动力学。大黄坏死因子对肿瘤生长的抑制与肿瘤蛋白水解的剂量依赖性增加有关，但肿瘤蛋白合成没有变化。在细胞水平上，rHuTNF对G2/M细胞具有显著的细胞抑制作用，并导致能够摄取BrdUrd的细胞比例显著降低。在rHuTNF输注开始时，仅在标记的肿瘤细胞中发现BrdUrd（细胞死亡指标）的释放。这些结果表明，肿瘤蛋白分解可能通过调节细胞质蛋白质量来影响细胞周期活动，或者当细胞分裂突然中断时，肿瘤蛋白水解可能是一种限制细胞质大小的补偿机制。
To determine the significance of protein breakdown in regulating tumor growth and to better understand the antitumor mechanism of tumor necrosis factor in vivo, we measured the effects of a 6-h constant intravenous infusion of human recombinant tumor necrosis factor-alpha (rHuTNF) on tumor protein metabolism and cell cycle kinetics in rats bearing the Walker-256 carcinosarcoma. Protein metabolism was investigated with the use of [14C]leucine infusion; estimates of tumor cell cycle kinetics were obtained in vivo by use of 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis by flow cytometry. Reduction in tumor growth by rHuTNF was associated with a dose-dependent increase in tumor proteolysis but no change in tumor protein synthesis. At the cellular level, rHuTNF had a significant cytostatic effect on G2/M cells and caused a marked decrease in the fraction of cells capable of BrdUrd uptake. Release of BrdUrd, an indicator of cell death, was noted in only 7.5% of tumor cells labeled at the beginning of rHuTNF infusion. These results suggest that either tumor protein breakdown may influence cell cycle activity by regulating cytoplasmic protein mass or that tumor proteolysis may be a compensatory mechanism for limiting cytoplasmic size when cellular division is interrupted suddenly.
肿瘤坏死因子协同增强针对 DNA 拓扑异构酶 II 的化疗药物的体外细胞毒性。
影响因子：
11.2
作者：
Alexander,RB;Nelson,WG;Coffey,DS
通讯作者：
Coffey,DS
影响因子：
5.6
作者：
G. C. Baxter;C. Stanners
通讯作者：
C. Stanners