دورية أكاديمية

Fisetin Inhibited Growth and Metastasis of Triple-Negative Breast Cancer by Reversing Epithelial-to-Mesenchymal Transition via PTEN/Akt/GSK3β Signal Pathway

التفاصيل البيبلوغرافية
العنوان: Fisetin Inhibited Growth and Metastasis of Triple-Negative Breast Cancer by Reversing Epithelial-to-Mesenchymal Transition via PTEN/Akt/GSK3β Signal Pathway
المؤلفون: Jie Li, Xia Gong, Rong Jiang, Dan Lin, Tao Zhou, Aijie Zhang, Hongzhong Li, Xiang Zhang, Jingyuan Wan, Ge Kuang, Hongyuan Li
المصدر: Frontiers in Pharmacology, Vol 9 (2018)
بيانات النشر: Frontiers Media S.A., 2018.
سنة النشر: 2018
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: fisetin, triple negative breast cancer, EMT, PTEN, AKT, Therapeutics. Pharmacology, RM1-950
الوصف: Triple negative breast cancer (TNBC), characterized by its highly aggressive and metastatic features, is associated with poor prognosis and high mortality partly due to lack of effective treatment. Fisetin, a natural flavonoid compound, has been demonstrated to possess anti-cancer effects in various cancers. However, the effects and mechanisms of fisetin on metastasis of TNBC remain uncovered. In this study, we found that fisetin dose-dependently inhibited cell proliferation, migration and invasion in TNBC cell lines MDA-MB-231 and BT549 cells. In addition, fisetin reversed epithelial to mesenchymal transition (EMT) as evaluated by cell morphology and EMT markers in MDA-MB-231 and BT549 cells. Furthermore, fisetin suppressed phosphoinositol 3-kinase (PI3K)-Akt-GSK-3β signaling pathway but upregulated the expression of PTEN mRNA and protein in a concentration-dependent manner. Further, silence of PTEN by siRNA abolished these benefits of fisetin on proliferation and metastasis of TNBCs. In vivo, using the metastatic breast cancer xenograft model bearing MDA-MB-231 cells, we found that fisetin dramatically inhibited growth of primary breast tumor and reduced lung metastasis, meanwhile, the expression of EMT molecules and PTEN/Akt/GSK-3β in primary and metastatic tissues changed in the same way as those in vitro experiments. In conclusion, all these results indicated that fisetin could effectively suppress proliferation and metastasis of TNBC and reverse EMT process, which might be mediated by PTEN/Akt/GSK-3β signaling pathway.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1663-9812
Relation: https://www.frontiersin.org/article/10.3389/fphar.2018.00772/full; https://doaj.org/toc/1663-9812
DOI: 10.3389/fphar.2018.00772
URL الوصول: https://doaj.org/article/726ad59b3b3f4d35b61ad3bcd2305626
رقم الأكسشن: edsdoj.726ad59b3b3f4d35b61ad3bcd2305626
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16639812
DOI:10.3389/fphar.2018.00772