Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Integr Cancer Ther. 2011 Dec;10(4):341-9. doi: 10.1177/1534735410384860. Epub 2010 Nov 8.
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.
本研究报告了从甘草中提取的类黄酮甘草素在人非小细胞肺癌 A549 细胞中的抗迁移、抗侵袭作用。甘草素通过降低 A549 细胞的迁移和侵袭，有效抑制了细胞转移。此外，甘草素还降低了 A549 介导的血管生成。进一步的研究表明，甘草素对癌症血管生成的抑制作用在裸鼠模型中也很明显。阻断 A549 细胞迁移与 ανβ3 整合素蛋白酶体降解增加有关。甘草素还降低了 FAK 和Src 的活性形式，并增加了失活磷酸化 Src（Tyr527）的水平，从而减少了 FAK 和 Src 的相互作用。甘草素抑制 FAK/Src 复合物也阻断了 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，甘草素可能是一种治疗肺癌的新型抗癌药物，可通过 3 种不同方式发挥作用：抑制迁移、侵袭和血管生成。
