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首页> 外文期刊>The Journal of Nutritional Biochemistry >Flaxseed oil enhances the effectiveness of trastuzumab in reducing the growth of HER2-overexpressing human breast tumors (BT-474)
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Flaxseed oil enhances the effectiveness of trastuzumab in reducing the growth of HER2-overexpressing human breast tumors (BT-474)

机译：亚麻籽油增强曲妥珠单抗在减少过度表达HER2的人乳腺肿瘤（BT-474）的生长中的功效

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摘要

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 FS0 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). FSOxTRAS 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. (C) 2015 Elsevier Inc. All rights reserved.
机译：亚麻籽油（FSO）可以降低管腔型乳腺癌动物模型中的乳腺肿瘤发生和HER2表达。 HER2过表达的肿瘤的主要治疗方法是曲妥珠单抗（TRAS）。我们旨在确定单独使用4％FSO并与TRAS联合使用对过表达HER2的肿瘤（BT-474）生长的影响，并探索潜在的机制，特别关注HER2，促分裂原激活的蛋白激酶（MAPK）和Akt信号传导，脂肪酸谱。给患有肿瘤的无胸腺小鼠喂食基础饮食（对照组）或4％FSO饮食，无论是否接受TRAS（1或2.5 mg / kg）治疗，持续4周。测量肿瘤生长，HER2信号生物标志物（mRNA和蛋白质）和脂肪酸谱。与对照组相比，仅用FS0治疗的肿瘤在肿瘤生长上没有差异。但是，与TRAS2.5和其他组相比，FSO + TRAS2.5导致肿瘤生长和细胞增殖明显降低，细胞凋亡增加，信号生物标志物表达（MAPK2，HER2 mRNA，pHER2蛋白）的降低幅度最大。 TRAS和FSO均具有减少Akt磷酸化/总表达和MAPK蛋白表达的主要作用。日粮FSO改变了肿瘤的脂肪酸谱。总之，仅4％的饮食FSO不会影响BT-474肿瘤的生长，但会增强TRAS（2.5 mg / kg）的减少肿瘤的作用。 FSOxTRAS相互作用的作用可以通过它们通过Akt和MAPK途径导致的HER2信号传导的组合减少来调节，从而导致细胞增殖减少和凋亡增加。 FSO改变了肿瘤脂肪酸谱，这可能有助于影响信号通路。这支持FSO作为用TRAS治疗的HER2 +乳腺癌的补充治疗。 （C）2015 Elsevier Inc.保留所有权利。

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