癌症研究
波形蛋白
自分泌信号
三阴性乳腺癌
旁分泌信号
上皮-间质转换
胰岛素样生长因子1受体
转移
蛋白激酶B
乳腺癌
癌症
生物
医学
生长因子
免疫学
信号转导
受体
内科学
细胞生物学
免疫组织化学
作者
Wei-Jen Chen,Jie-Heng Tsai,Li-Sung Hsu,Chih-Li Lin,Hui-Mei Hong,Min-Hsiung Pan
出处
期刊:Journal of Food and Drug Analysis
[The Journal of Food and Drug Analysis (JFDA), Food and Drug Administration, Taiwan (TFDA)]
日期:2021-03-15
卷期号:29 (1): 98-112
被引量:1
标识
DOI:10.38212/2224-6614.3090
摘要
The cancer-preventive activities of quercetin have been extensively studied in invasive breast cancer; however, the role of quercetin on triple-negative breast cancer (TNBC) with overexpression of insulin-like growth factor-1 receptor (IGF1R) has not been resolved. In this article, we demonstrated that quercetin inhibited the activation of IGF1R and its downstream kinases Akt and Erk1/2 in a dose-dependent manner in human MDA-MB-231 breast cancer cells (TNBC cell line). Related to this, quercetin markedly suppressed the metastatic phenotype and epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells by inhibiting the expression of EMT transcription factors Snail and Slug. Quercetin also increased the secretion of IGF-binding protein-3 in the conditioned medium of MDA-MB-231 cells while reducing the secretion of IGF1; thus, quercetin interrupted the autocrine or paracrine loop of IGF1 signaling. In xenograft mouse models, the administration of quercetin blocked the growth of MDA-MB-231 tumor xenografts and their lung metastasis, accompanied by the inactivation of IGF1R and the downregulation of the expression of Snail, Slug, and mesenchymal markers fibronectin and vimentin. These results suggest that quercetin has cancer-preventive value for TNBC by inhibiting IGF1/IGF1R signaling and preventing the consequent EMT and metastasis of TNBC.
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