Ophiopogonin B Inhibits Migration And Invasion In Non-Small Cell Lung Cancer Cells Through Enhancing The Interaction Between Axin And Beta-Catenin

Ophiopogonin B (OP-B), a kind of saponin compound that exists in Radix Ophiopogonis is frequently adopted for the treatment of lung disease as traditional Chinese medicine. The present work aimed to explore the anti-tumor activity of OP-B on non-small cell lung carcinoma (NSCLC) and its possible mechanism. We found that OP-B-treated cells suppressed the viability and proliferation of cells depending on its concentration, as assayed by MTT and Alamar Blue (IC50 were 14.22 +/- 1.94, 12.14 +/- 2.01, and 16.11 +/- 1.83 mu M in A549, NCI-H1299, and NCI-H460 cells, respectively). Then, the suppressive effect of OP-B on the invasion and migration of NSCLC was observed through wound healing and Transwell assays, and the epithelial-mesenchymal transition (EMT) markers was detected by immunofluorescence and western blotting. In addition, a dose-dependent reduction of beta-catenin both within cytoplasm and nucleus was observed, and the downstream proteins cyclin D1 and c-Myc of Wnt/beta-catenin pathway were also reduced. We further constructed beta-catenin-overexpression cell models to reveal the underlying mechanism. The results showed that 10 mu M of OP-B notably reduced beta-catenin protein levels, as well as cell migration and invasion. In spite of the increasement of beta-catenin, activation of Wnt pathway and EMT progression, knockdown of Axin leaded to de-function of OP-B on cell metastasis. Taken together, OP-B reduced NSCLC migration and invasion by strengthening the Axin/beta-catenin interaction and reducing beta-catenin protein translocation.