Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non–Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway

Integrative Cancer Therapies - Tập 10 Số 4 - Trang 341-349 - 2011
Yu-Chen Tsai1, Chih‐Jen Yang2,1,3, Ya‐Ling Hsu3, Ling‐Yu Wu3, Yu‐Chieh Tsai3, Chi‐Tun Lien1, Ming‐Shyan Huang2,1, Po‐Lin Kuo2,4,5
1Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
2Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
5Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Tóm tắt

This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non–small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin’s inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.

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Integrative Cancer Therapies

Tập 10 Số 4

341-349

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