Key findings:
In previous research by this group, established estrogen receptor (ER) positive (MCF7) human breast tumors in the athymic mouse model have been shown to be reduced by flaxseed, flax oil and SDG. The authors have shown one plausible mechanisms as a reduction in the expression and activity of the human epidermal growth factor receptor 2 (HER2). In this study, over short and longer term, flaxseed did not interfere with the action of trastuzumab, the primary treatment for HER2 overexpressing tumors. In early stages, flaxseed decreased tumor size but not in the long term and did improve overall survival – either alone or with TRAS.
ABSTRACT:
Flaxseed (FS) reduces breast tumorigenesis and human epidermal growth factor receptor 2 (HER2) expression in post menopausal patients and animal models. The primary treatment for HER2 overexpressing tumors is trastuzumab (TRAS). FS oil enhances TRAS effectiveness in athymic mice but the FS effect is unknown and was therefore determined. Athymic mice with established BT 474 tumors were fed the basal diet (control), or 10 per cent FS diet, with or without TRAS (2.5mg per kg) treatment for 5 wk. After 2 wk, TRAS and FS reduced tumor size with a trend for an FS × TRAS interaction; however, after 5 wk, only TRAS reduced tumor size and increased tumor apoptosis. FS did not further improve TRAS effect but increased overall survival. TRAS reduced signaling biomarkers [phosphorylated HER 2 and mitogen activated protein kinase (MAPK) proteins; Akt1, Akt2, MAPK, and estrogen receptor α mRNA], FS reduced phosphorylated Akt1 protein, and FS × TRAS interactions were seen for HER2 mRNA and phosphorylated Akt1 protein. FS, with and without TRAS, increased tumor n 3 PUFA levels and serum lignans indicating potential roles in the observed effect. In conclusion, TRAS reduces tumor growth by influencing HER2 signaling. Dietary FS has minimal tumor reducing effect, does not interfere with TRAS action, but improves overall survival in athymic mice. (Authors Abstract)
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