Cachexia, a negative prognostic factor, worsens a patient's quality of life. We established 2 novel
cachexia models with the human
stomach cancer cell line MKN-45, which was subcloned to produce potent
cachexia-inducing cells by repeating the xenografts in immune-deficient mice. After subsequent xenografts, we isolated potent
cachexia-inducing cells (MKN45cl85 and 85As2mLuc). Xenografts of MKN45cl85 cells in mice led to substantial
weight loss and reduced adipose tissue and musculature volumes, whereas xenografts of 85As2mLuc cells resulted in highly metastatic and cachectic mice. Surgical removal of
tumor tissues helped the mice regain
body-weight in both mouse models. In vitro studies using these cells showed that
isoflavones reduced their proliferation, implying that the
isoflavones possess antiproliferative effects of these
cancer cell lines.
Isoflavone treatment on the models induced
tumor cytostasis, attenuation of
cachexia, and prolonged survival whereas discontinuation of the treatment resulted in progressive
tumor growth and
weight loss. The inhibitory effects of
tumor growth and
weight loss by
isoflavones were graded as
soy isoflavone aglycone AglyMax >
daidzein >
genistein. These results demonstrated that the 2 novel cachectic mouse models appear useful for analyzing the mechanism of
cancer cachexia and monitoring the efficacy of anticachectic agents.