Our previous short-term study has shown that 10% flaxseed (FS) inhibits the growth of human
estrogen dependent
estrogen receptor positive
breast tumors (MCF-7) xenografts in ovariectomized (OVX) athymic mice and enhances the
tumor inhibitory effect of
tamoxifen (TAM). This study determined the long-term effect of 5% and 10% FS, with or without TAM, on the growth of MCF-7 xenografts in athymic mice and the potential mechanisms of actions. OVX mice with established MCF-7
tumors were treated with basal diet (control), 5% FS (5FS), 10% FS (10FS), and TAM (5 mg/pellet, 60-day release), alone or in combination, for 16 wk without
estrogen supplementation.
Tumor growth was monitored weekly. At sacrifice, the
tumors were analyzed by immunohistochemistry for cell proliferation, apoptosis, and expression of
estrogen-related genes and signal transduction pathways. Both 5FS and 10FS regressed the pretreatment
tumor size by over 90% similar to control. TAM initially regressed the
tumors but then induced a regrowth; thus, only a final 6% reduction from pretreatment
tumor size was achieved, which was attenuated by combining TAM with 10FS but not with 5FS. TAM combined with 10FS regressed
tumors to 55% of pretreatment
tumor size due to decreased cell proliferation and increased apoptosis. The expressions of
cyclin D1,
estrogen receptor alpha, human epidermal growth factor receptor 2, and
insulin-like growth factor I receptor in the TAM group were significantly reduced when TAM was combined with 5FS or 10FS. In conclusion, after long-term treatment, FS did not stimulate
tumor growth and combined with TAM, regressed
tumor size in part due to downregulation of the expression of
estrogen-related gene products and signal transduction pathways.