Key Findings:
Trastuzumab (TRAS, Herceptin), used as a treatment for HER2 positive (HER2 plus) breast cancer was tested with or without flax oil. A reduction in tumor growth and the expression of HER2 and growth factor receptor signaling pathways in addition to increased effectiveness of TRAS in HER2(+) cancer was found following flax oil feeding (4 per cent). Flax oil had no effect on tumor growth, cell proliferation or apoptosis, but did increase ALA, EPA and FHA levels in BT-474 tumors. The latter effects may contribute to the anticancer actions of flax oil in breast cancer.
ABSTRACT:
Flaxseed oil (FSO) reduces breast tumorigenesis and HER2 expression in animal models of luminal breast cancer. The primary treatment for HER2- overexpressing tumors is trastuzumab (TRAS). We aimed to determine the effect of 4 per cent FSO alone and combined with TRAS on HER2-overexpressing tumor growth and to explore potential mechanisms with a specific focus on HER2, mitogen-activated protein kinase (MAPK) and Akt signaling and fatty acid profile. Athymic mice with established tumors were fed the basal diet (control) or 4 per cent FSO diet, with or without TRAS (1 or 2.5 mg per kg) treatment for 4 weeks. Tumor growth, HER2 signaling biomarkers (mRNA and protein) and fatty acid profile were measured. Tumors treated with FSO alone showed no difference in tumor growth compared to control; however, compared to TRAS2.5 and other groups, FSO plus TRAS2.5 caused significantly lower tumor growth and cell proliferation and higher apoptosis and the greatest lowering of signaling biomarker expressions (MAPK2, HER2 mRNA; pHER2 protein). Both TRAS and FSO had main effects of reducing the phosphorylated/total expression of Akt and MAPK protein expression. Dietary FSO altered the tumor fatty acid profile. In conclusion, 4 per cent dietary FSO alone does not affect BT minus 474 tumor growth but enhances the tumor-reducing effect of TRAS (2.5 mg per kg). FSO plus TRAS interactive effect may be modulated by their combined reductions of HER2 signaling through the Akt and MAPK pathways leading to reduced cell proliferation and increased apoptosis. FSO alters tumor fatty acid profile that likely contributes to effects on signaling pathways. This supports FSO as a complementary treatment for HER2 plus breast cancer treated with TRAS. (Authors Abstract)