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首页> 外文期刊>International Journal of Environmental Research and Public Health >Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1
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Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1

机译：甘油I通过ZEB1逆转来曲唑抗性乳腺癌的上皮向间质转化。

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Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a ?3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.
机译：尽管芳香酶抑制剂是绝经后早期转移性雌激素依赖性乳腺癌女性的标准内分泌治疗药物，但它们受到耐药性发展的限制。对此过程的更好理解对于设计新颖的疾病管理策略至关重要。以前，我们证明了与激素独立性，增强的细胞运动性和上皮间充质转化（EMT）相关的来曲唑抗性的全球蛋白质组学特征。耐来曲唑耐药性乳腺癌细胞（LTLT-Ca）用新型植物抗毒素，糖精I进行处理，并表现出与上皮表型同义的形态特征，并减少了增殖。耐来曲唑抗性增加了锌指E-Box结合Homeobox 1（ZEB1）的表达（4.51倍），而甘油I的处理则降低了约3.39倍。免疫荧光分析结果表明，甘油I分别诱导E-钙粘蛋白和ZEB1的增加和减少。在切除卵巢的雌性裸鼠体内进行的研究表明，用甘油甘油处理的肿瘤对ZEB1和N-钙粘蛋白的染色较弱，对E-钙粘蛋白的染色较深。与来曲唑敏感性细胞相比，LTLT-Ca细胞显示出增强的运动能力，但是在存在糖精I的情况下，其侵袭和迁移分别降低了68％和83％。甘油三醇I的这些作用部分是通过抑制ZEB1介导的，因此表明甘油三醇I在靶向来曲唑耐药的乳腺癌中靶向EMT的治疗潜力。

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