Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non-Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway
Glabridin Inhibits Migration, Invasion, and Angiogenesis of Human Non-Small Cell Lung Cancer A549 Cells by Inhibiting the FAK/Rho Signaling Pathway
复制标题
DOI：
10.1177/1534735410384860
复制
发表时间：
2011-12-01
影响因子：
2.9
通讯作者：
Kuo, Po-Lin
中科院分区：
文献类型：
--
作者：
Tsai, Ying-Ming;Yang, Chih-Jen;Kuo, Po-Lin
本文报道甘草黄酮类化合物光甘草定对人非小细胞肺癌A549细胞的抗迁移、抗侵袭作用。光甘草定通过抑制A549细胞的迁移和侵袭而有效抑制细胞转移。此外，光甘草定还减少A549介导的血管生成。进一步的研究表明，光甘草定对肿瘤血管生成的抑制作用在裸鼠模型中也很明显。A549细胞迁移的阻断与α nu β 3整合素蛋白体降解的增加相关。Glabridin还降低了FAK和Src的活性形式，并提高了失活的磷酸化Src（Tyr 527）的水平，降低了FAK和Src的相互作用。光甘草定对FAK/Src复合物的抑制也阻断了Akt的激活，导致RhoA和肌球蛋白轻链磷酸化的激活减少。这项研究表明，光甘草定可能是一种新的抗癌剂，用于治疗肺癌的3种不同的方式：抑制迁移，侵袭和血管生成。
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 alpha nu beta 3 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.