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白细胞介素-6对癌症恶病质影响的实验研究

Experimental study of the effect of IL-6 on cancer cachexia.

作者信息

Ikeda T, Nishiguchi Y, Chung Y, Yamada N, Sowa M

机构信息

OSAKA CITY UNIV,SCH MED,DEPT SURG 1,ABENO KU,OSAKA 545,JAPAN.

出版信息

Oncol Rep. 1997 Sep-Oct;4(5):921-6. doi: 10.3892/or.4.5.921.

DOI:10.3892/or.4.5.921
PMID:21590167
Abstract

Several cytokines, including IL-1, TNF, LIF and IL-6 have recently been proposed as cachexia inducers. We experimentally examined the participation of cytokines, particularly, IL-6, in cancer cachexia using the human digestive cancer cell lines MKN 28, MKN 45, MKN 74, Kato-III, OCUM-2M (gastric cancer), SW1990, Panc-1 (pancreatic cancer), and OCUG (gallbladder cancer). A high level of IL-6 was detected in the OCUG culture medium. Nude mice bearing OCUG tumor had reduced body weight even when the tumor was relatively small. Loss of both muscle and adipose tissue, anemia, hypoglycemia, and a high serum level of human IL-6 were observed in these mice. However, body weight recovered rapidly to the level of that of nontumor-bearing mice after resection of OCUG tumor. Antihuman IL-6 but not anti-murine IL-6 receptor antibodies significantly suppressed the development of cachexia as measured by various indicators of cachexia including loss of both muscle and adipose tissue, anemia and hypoglycemia, as well as weight loss. These results suggest that OCUG-bearing mice exhibited cancer cachexia mediated by IL-6, and that of OCUG cell line might be useful as a human digestive cancer cachexia model.

摘要

最近,包括白细胞介素-1(IL-1)、肿瘤坏死因子(TNF)、白血病抑制因子(LIF)和白细胞介素-6(IL-6)在内的几种细胞因子被认为是恶病质诱导剂。我们使用人类消化癌细胞系MKN 28、MKN 45、MKN 74、Kato-III、OCUM-2M(胃癌)、SW1990、Panc-1(胰腺癌)和OCUG(胆囊癌),通过实验研究了细胞因子,特别是IL-6在癌症恶病质中的作用。在OCUG培养基中检测到高水平的IL-6。携带OCUG肿瘤的裸鼠即使在肿瘤相对较小时体重也会减轻。在这些小鼠中观察到肌肉和脂肪组织丢失、贫血、低血糖以及血清中人IL-6水平升高。然而,切除OCUG肿瘤后,体重迅速恢复到未携带肿瘤小鼠的水平。抗人IL-6抗体而非抗鼠IL-6受体抗体通过包括肌肉和脂肪组织丢失、贫血和低血糖以及体重减轻在内的各种恶病质指标,显著抑制了恶病质的发展。这些结果表明,携带OCUG肿瘤的小鼠表现出由IL-6介导的癌症恶病质,并且OCUG细胞系可能作为人类消化癌恶病质模型有用。

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