J Cancer 2021; 12(20):6274-6284. doi:10.7150/jca.60066 This issue

Research Paper

Ophiopogonin B inhibits migration and invasion in non-small cell lung cancer cells through enhancing the interaction between Axin and β-catenin

Shiping Zhang1,2, Hongxiao Li1, Liqiu Li1, Qian Gao1, Ling Gu1, Cheng Hu1, Meijuan Chen1✉, Xu Zhang1✉

1. School of Medicine &Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, P.R. China
2. Health center, Nanjing University of Chinese Medicine, Nanjing, 210023, P.R. China

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Citation:
Zhang S, Li H, Li L, Gao Q, Gu L, Hu C, Chen M, Zhang X. Ophiopogonin B inhibits migration and invasion in non-small cell lung cancer cells through enhancing the interaction between Axin and β-catenin. J Cancer 2021; 12(20):6274-6284. doi:10.7150/jca.60066. Available from https://www.jcancer.org/v12p6274.htm

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Abstract

Graphic 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 μM 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 β-catenin both within cytoplasm and nucleus was observed, and the downstream proteins cyclin D1 and c-Myc of Wnt/β-catenin pathway were also reduced. We further constructed β-catenin-overexpression cell models to reveal the underlying mechanism. The results showed that 10 μM of OP-B notably reduced β-catenin protein levels, as well as cell migration and invasion. In spite of the increasement of β-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/β-catenin interaction and reducing β-catenin protein translocation.

Keywords: non-small cell lung cancer cells (NSCLC), migration, invasion, Wnt/β-catenin pathway, EMT