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% FSO alone and combined with TRAS on HER2-overexpressing
tumor (BT-474) 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% FSO diet, with or without TRAS (1 or 2.5 mg/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+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% dietary FSO alone does not affect BT-474
tumor growth but enhances the
tumor-reducing effect of TRAS (2.5 mg/kg). FSO×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+
breast cancer treated with TRAS.