Rebeca Rosilene, Bracht Lívia, Noleto Guilhermina Rodrigues, Martinez Glaucia Regina, Cadena Silvia Maria Suter Correia, Carnieri Eva Gunilla Skare, Rocha Maria Eliane Merlin, de Oliveira Maria Benigna Martinelli
Department of Biochemistry, UFPR-Federal University of Paraná, Curitiba, CEP, PR, Brazil.
Cell Biochem Funct. 2008 Aug;26(6):731-8. doi: 10.1002/cbf.1497.
In neoplasic cachexia, chemical mediators seem to act as initiators or perpetuators of this process. Walker 256 cells, whose metabolic properties have so far been little studied with respect to cancer cachexia, are used as a model for the study of this syndrome. The main objective of this research was to pinpoint the substances secreted by these cells that may contribute to the progression of the cachectic state. Since inflammatory mediators seem to be involved in the manifestation of this syndrome, the in vitro production of nitric oxide (NO), cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)), and prostaglandin E2 (PGE2) was evaluated in Walker 256 cells isolated from ascitic tumors. After 4 or 5 h, a significant increase in NO production was observed (2.55 +/- 1.56 and 4.05 +/- 1.99 nmol NO per 10(7) cells, respectively). When isolated from a 6-day-old tumor, a significantly lower production of IL-6 and higher production of TNF-alpha than in cells from a 4-day-old tumor were observed, indicating a relationship between the production of cytokines and the time of tumor development after implantation. Considerable production of PGE(2) by Walker 256 cells isolated from the 6-day-old tumor was also observed. Polyamines were also determined in Walker 256 cells. Levels of putrescine, spermidine, and spermine did not show significant differences in tumors developed during 4 or 6 days. Direct evidence of the release of proinflammatory cytokines and PGE2 by Walker 256 cells suggests that these mediators can drive the cachectic syndrome in the host, the effect being dependent on tumor development time.
在肿瘤性恶病质中，化学介质似乎是这一过程的启动者或推动者。沃克256细胞的代谢特性迄今在癌症恶病质方面研究较少，被用作研究该综合征的模型。本研究的主要目的是确定这些细胞分泌的可能导致恶病质状态进展的物质。由于炎症介质似乎参与了该综合征的表现，因此对从腹水肿瘤中分离出的沃克256细胞中一氧化氮（NO）、细胞因子（肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6））以及前列腺素E2（PGE2）的体外产生进行了评估。4或5小时后，观察到NO产生显著增加（分别为每10(7)个细胞2.55±1.56和4.05±1.99 nmol NO）。当从6日龄肿瘤中分离时，观察到IL-6产生显著低于4日龄肿瘤细胞，而TNF-α产生高于4日龄肿瘤细胞，这表明细胞因子产生与植入后肿瘤发展时间之间存在关联。还观察到从6日龄肿瘤中分离出的沃克256细胞大量产生PGE(2)。还测定了沃克256细胞中的多胺。腐胺、亚精胺和精胺水平在4天或6天内形成的肿瘤中未显示出显著差异。沃克256细胞释放促炎细胞因子和PGE2的直接证据表明，这些介质可驱动宿主的恶病质综合征，其效应取决于肿瘤发展时间。
