Mori Kazushige, Fujimoto-Ouchi Kaori, Onuma Etsuro, Noguchi Mariko, Shimonaka Yasushi, Yasuno Hideyuki, Nishimura Takashi
Department of Product Research, Chugai Pharmaceutical Co., Ltd., Kamakura, Japan.
Biomed Res. 2009 Feb;30(1):47-51. doi: 10.2220/biomedres.30.47.
We established models of cancer-related anemia in mice from subcutaneous inoculation of two IL-6-producing cancer cell lines, human lung cancer cell line LC-06-JCK and murine colon26 clone 5 colon cancer cells. In both models, elevated levels of IL-6 were detected in sera and hemoglobin levels significantly decreased compared with non-tumor-bearing mice. In the LC-06-JCK model, serum albumin levels also decreased with elevated levels of human IL-6 in sera. On the other hand, serum levels of EPO increased, although anemia developed and did not improve. The development of cancer-related anemia was prevented by the administration of a rat anti-mouse IL-6 receptor antibody, MR16-1, in the LC-06-JCK model. It is therefore suggested that IL-6 causes anemia independent of a reduction in EPO levels. Our preclinical models should be useful for exploring new modalities for the treatment of cancer-related anemia.
我们通过皮下接种两种产生白细胞介素-6(IL-6)的癌细胞系,即人肺癌细胞系LC-06-JCK和小鼠结肠26克隆5结肠癌细胞,建立了小鼠癌症相关性贫血模型。在这两种模型中,与未荷瘤小鼠相比,血清中IL-6水平升高,血红蛋白水平显著降低。在LC-06-JCK模型中,血清白蛋白水平也随着血清中人IL-6水平的升高而降低。另一方面,尽管发生了贫血且未改善,但促红细胞生成素(EPO)的血清水平升高。在LC-06-JCK模型中,给予大鼠抗小鼠IL-6受体抗体MR16-1可预防癌症相关性贫血的发生。因此,提示IL-6导致贫血与EPO水平降低无关。我们的临床前模型对于探索治疗癌症相关性贫血的新方法应该是有用的。