title: Dietary flaxseed-trastuzumab interactive effects on the growth of HER2-overexpressing human breast tumors (BT-474).
abstract: Flaxseed (FS) reduces breast tumorigenesis and human epidermal growth factor receptor 2 (HER2) expression in postmenopausal 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% FS diet, with or without TRAS (2.5mg/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 HER2 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.affiliation: Department of Nutritional Sciences, Faculty of Medicine, Toronto, Ontario, Canada.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Mason
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Fu
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yu
authors.forename: Lilian U
authors.initials: LU
authors.lastname: Thompson
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents; D017209:Apoptosis; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D019597:Flax; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005227:Fatty Acids; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D000068878:Trastuzumab