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Alpha ‐ linolenic acid (ALA)‐ rich flaxseed oil (FO) enhances the effectiveness of trastuzumab (TRAS) in reducing the growth of HER2 overexpressing human breast cancer tumors (BT‐474)
Author(s) -
Mason Julie Kathleen,
Truan Jennifer S,
Thompson Lilian U,
Chen Jianmin
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.897.10
Subject(s) - medicine , trastuzumab , breast cancer , cancer
TRAS is the primary drug for breast tumors that overexpress epidermal growth factor receptor 2 (HER2) but tumors develop resistance within 1 year of treatment. Our objective is to determine whether combining dietary ALA‐rich FO with TRAS treatment will enhance TRAS effectiveness. HER2 overexpressing breast tumor cells (BT‐474) were tested for proliferation and HER2 level in vitro after treatment with ALA (50µM), TRAS (10µg/ml) or their combination. Compared with untreated control, ALA, TRAS and combination caused a 35%, 54% and 61% reduction in proliferation and a 23% increase and 19% and 88% reduction in HER 2 expression (p<0.05), respectively. Ovariectomized mice with BT‐474 tumors were fed the basal diet (BD) (control) or treated with TRAS (2.5 or 5mg/kg) and fed either the BD or BD supplemented with 8% FO for 4 weeks. Compared to control, both TRAS and FO+TRAS treatments caused significant reductions in tumor growth over time (P<0.05). Control tumors increased in size by 63% while tumor size with FO+TRAS2.5 was reduced by 85% which is greater than that with TRAS2.5 (16%) (p<0.05) and not significantly different from that with TRAS5, alone or with FO. FO+TRAS2.5 caused greater reduction ( 85%) in cell proliferation (Ki67 labeling index) than with TRAS2.5 alone (59%; p<0.05). In conclusion, ALA and ALA‐rich FO enhanced TRAS effects and combined FO and low dose TRAS was just as effective as high dose TRAS. Grant Funding Source NSERC