TY - JOUR AB - Epithelial-mesenchymal transition (EMT) is a pivotal event in tumor progression during which cancer cells undergo dramatic changes acquiring highly invasive properties. In this study, we found that nobiletin, a polymethoxylated flavone, suppressed migration and invasion in both U87 and U251 glioma cells. Expression of epithelial markers (E-cadherin and occludin) was upregulated; mesenchymal markers (N-cadherin, fibronectin) and the transcriptional factor Slug were downregulated after nobiletin treatment. Transforming growth factor β (TGF-β) was applied to stimulate EMT and the results showed that nobiletin not only influenced basal level cell migration but also prevented TGF-β-triggered migration and EMT, with the AKT/GSK3β/β-catenin signaling pathway greatly involved. Furthermore, nobiletin remarkably diminished TGF-β-induced β-catenin nuclear translocation and the binding to the Slug promoter. It is worth noting that nobiletin almost blocked invasion in Slug-expressing U87 and U251 cells, and only exhibiting faint effect on non-Slug-expressing U343 glioma cells. Reinforced Slug expression in U343 cells by transfecting Slug plasmid was significantly attenuated by nobiletin, demonstrating the essential role of Slug in the anti-metastasis effect of nobiletin. Nobiletin repressed tumor growth in vivo and abrogated EMT in nude mice bearing U87-Luc xenografts, as demonstrated by Xenogen IVIS imaging and immunohistochemistry assay. Our findings suggested that nobiletin might have a great potential for treating glioblastoma. AD - Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China AU - Zhang,Xiang AU - Zheng,Kebin AU - Li,Chunhui AU - Zhao,Yonghui AU - Li,Heyang AU - Liu,Xuguang AU - Long,Yinbo AU - Yao,Junchao DA - 2017/05/01 DO - 10.3892/or.2017.5522 EP - 2856 IS - 5 JO - Oncol Rep KW - nobiletin AKT/GSK3β/β-catenin Slug glioma invasion PY - 2017 SN - 1021-335X 1791-2431 SP - 2847 ST - Nobiletin inhibits invasion via inhibiting AKT/GSK3β/β-catenin signaling pathway in Slug-expressing glioma cells T2 - Oncology Reports TI - Nobiletin inhibits invasion via inhibiting AKT/GSK3β/β-catenin signaling pathway in Slug-expressing glioma cells UR - https://doi.org/10.3892/or.2017.5522 VL - 37 ER -