Metastasis is the major cause of death from lung cancer. Quercetin, a widely distributed bioflavonoid, is well known to induce growth inhibition in a variety of human cancer cells, but how it affects lung cancer cell invasion and metastasis is unclear. Herein, we found that quercetin inhibited the migration/invasion of non-small cell lung cancer (NSCLC) cell lines and bone metastasis in an orthotopic A549 xenograft model by suppressing the Snail-mediated epithelial-to-mesenchymal transition (EMT). Moreover, survival times of animals were also prolonged after quercetin treatment. Mechanistic investigations found that quercetin suppressed Snail-dependent Akt activation by upregulating maspin and Snail-independent a disintegrin and metalloproteinase (ADAM) 9 expression pathways to modulate the invasive ability of NSCLC cells. In clinical samples, we observed that patients with Snailhigh/p-Akthigh tumors had the shortest survival times. In addition, a lower survival rate was also found in ADAM9high patients than in ADAM9low patients. Overall, our results provide new insights into the role of quercetin-induced molecular regulation in suppressing NSCLC metastasis and suggest that quercetin has potential therapeutic applications for metastatic NSCLC.
|頁（從 - 到）||1746-1758|
|期刊||Biochimica et Biophysica Acta - Molecular Cell Research|
|出版狀態||已發佈 - 十月 1 2017|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Chang, J. H., Lai, S. L., Chen, W. S., Hung, W. Y., Chow, J. M., Hsiao, M., Lee, W. J., & Chien, M. H. (2017). Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways. Biochimica et Biophysica Acta - Molecular Cell Research, 1864(10), 1746-1758. https://doi.org/10.1016/j.bbamcr.2017.06.017