Lim Won-Chul, Kim Hyunhee, Kim Young-Joo, Choi Kyung-Chul, Lee In Ho, Lee Ki Heon, Kim Mi Kyung, Ko Hyeonseok
Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, College of Medicine, Dankook University, Seoul, South Korea.
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.
Bioorg Med Chem Lett. 2017 Aug 1;27(15):3342-3348. doi: 10.1016/j.bmcl.2017.06.014. Epub 2017 Jun 3.
Epithelial-to-mesenchymal transition (EMT), an important cellular process, occurs during cancer development and progression, has a crucial role in metastasis by enhancing the motility of tumor cells. Dioscin is a polyphenolic component isolated from Phyllanthus amarus, which exhibits a wide range of pharmacological and physiological activities, such as anti-tumor, anti-inflammatory, anti-obesity, anti-fungal, and anti-viral activities. However, the possible role of dioscin in the EMT is unclear. We investigated the suppressive effect of dioscin on the EMT. Transforming growth factor-beta 1 (TGF-β1) is known to induce EMT in a number of cancer cell types and promote lung adenocarcinoma migration and invasion. To verify the inhibitory role of dioscin in lung cancer migration and invasion, we investigated the use of dioscin as inhibitors of TGF-β1-induced EMT in A549 lung cancer cells in vitro. Here, we found that dioscin prominently increased expression of the epithelial marker E-cadherin and expression of the mesenchymal marker N-cadherin and Snail during the TGF-β1-induced EMT. In addition, dioscin inhibited the TGF-β1-induced increase in cell migration and invasion of A549 lung cancer cells. Also, dioscin remarkably inhibited TGF-β1-regulated activation of MMP-2/9, Smad2, and p38. Taken together, our findings provide new evidence that dioscin suppresses lung cancer migration, and invasion in vitro by inhibiting the TGF-β1-induced EMT.
上皮-间质转化（EMT）是一个重要的细胞过程，发生在癌症的发展和进程中，通过增强肿瘤细胞的运动性在转移中起关键作用。薯蓣皂苷是从苦味叶下珠中分离出的一种多酚类成分，具有广泛的药理和生理活性，如抗肿瘤、抗炎、抗肥胖、抗真菌和抗病毒活性。然而，薯蓣皂苷在EMT中的可能作用尚不清楚。我们研究了薯蓣皂苷对EMT的抑制作用。已知转化生长因子-β1（TGF-β1）可在多种癌细胞类型中诱导EMT，并促进肺腺癌的迁移和侵袭。为了验证薯蓣皂苷在肺癌迁移和侵袭中的抑制作用，我们在体外研究了薯蓣皂苷作为TGF-β1诱导的A549肺癌细胞EMT抑制剂的作用。在此，我们发现薯蓣皂苷在TGF-β1诱导的EMT过程中显著增加了上皮标志物E-钙黏蛋白的表达，同时降低了间质标志物N-钙黏蛋白和Snail的表达。此外，薯蓣皂苷抑制了TGF-β1诱导的A549肺癌细胞迁移和侵袭的增加。而且，薯蓣皂苷显著抑制了TGF-β1调节的MMP-2/9、Smad2和p38的激活。综上所述，我们的研究结果提供了新的证据，表明薯蓣皂苷通过抑制TGF-β1诱导的EMT来抑制肺癌的体外迁移和侵袭。
