Nobiletin inhibited hypoxia-induced epithelial-mesenchymal transition of lung cancer cells by inactivating of Notch-1 signaling and switching on miR-200b.

摘要: Abstract Epithelial-mesenchymal transition (EMT) is an early step in the process of tumor metastasis. It well known that microenvironment affects malignancy various carcinomas; particular, hypoxia induces EMT. Deregulated notch signaling also contributes a lot to development EMT lung cancer. In this study, we investigated use Notch-1-inhibiting compound as novel therapeutic candidates regulate hypoxia-induced cancer cells. According previous screening, nobiletin was selected Notch-1 inhibitor. Hypoxia-induced characteristic increased N-cadherin & vimentin expressions and decreased E-cadherin expressions. Treatment with notably attenuated EMT, invasion migration H1299 cells, accompanied reduced Notch-1, Jagged1/2 its downstream genes Hey-1 Hes-1. Nobiletin treatment promoted tumorsuppressive miR-200b level. Moreover, notch-1 siRNA prevented hypoxia-mediated cell Twist1, Snail1, ZEB1/2 expressions, which are key markers. Re-expression blocked invasion. Our findings suggest downregulation reexpression by might be remedy for therapy