Ophiopogonin B inhibits migration and invasion in non-small cell lung cancer cells through enhancing the interaction between Axin and β-catenin
Shiping Zhang, Hongxiao Li, Liqiu Li, Qian Gao, Ling Gu, Cheng Hu, Meijuan Chen, Xu Zhang
Abstract
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 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 -catenin both within cytoplasm and nucleus was observed, and the downstream proteins cyclin D1 and c-Myc of Wnt/-catenin pathway were also reduced. We further constructed -catenin-overexpression cell models to reveal the underlying mechanism. The results showed that 10 M of OP-B notably reduced -catenin protein levels, as well as cell migration and invasion. In spite of the increasement of -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/-catenin interaction and reducing -catenin protein translocation.