Chen Xiangni, Yan Ning
Department of Hepatology.
Department of Preventive Treatment, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, China.
Anticancer Drugs. 2021 Sep 1;32(8):786-792. doi: 10.1097/CAD.0000000000001066.
Stachydrine is a bioactive alkaloid that has been found to exert tumor-suppressive potential. However, the effect of stachydrine on hepatocellular carcinoma (HCC) has not been previously investigated. In the present study, we investigated the effect of transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in HepG2 cells. Our results showed that stachydrine significantly suppressed TGF-β1-induced HepG2 cell migration and invasion in a dose-dependent manner. Stachydrine prevented TGF-β1-induced EMT in HepG2 cells, as proved by the increased expression level of E-cadherin and decreased expression levels of N-cadherin and vimentin. In addition, stachydrine attenuated TGF-β1-induced upregulation of TGF-β receptor I (TβRI) in both protein and mRNA levels. Further mechanism investigations proved that stachydrine prevented TGF-β1-induced activation of Smad2/3 and phosphoinositol-3-kinase (PI3K)/Akt/mTOR signaling pathways in HepG2 cells. In conclusion, these findings demonstrated that stachydrine prevented TGF-β1-induced EMT in HCC cells through Smad2/3 and PI3K/Akt/mTOR signaling pathways. Thus, stachydrine might be a potential therapeutic agent for the treatment of HCC.
水苏碱是一种具有生物活性的生物碱，已被发现具有肿瘤抑制潜力。然而，水苏碱对肝细胞癌（HCC）的影响此前尚未得到研究。在本研究中，我们研究了转化生长因子-β1（TGF-β1）诱导的HepG2细胞上皮-间质转化（EMT）的影响。我们的结果表明，水苏碱以剂量依赖的方式显著抑制TGF-β1诱导的HepG2细胞迁移和侵袭。水苏碱可防止TGF-β1诱导的HepG2细胞发生EMT，这可通过E-钙黏蛋白表达水平升高以及N-钙黏蛋白和波形蛋白表达水平降低得到证明。此外，水苏碱在蛋白质和mRNA水平上均减弱了TGF-β1诱导的TGF-β受体I（TβRI）上调。进一步的机制研究证明，水苏碱可防止TGF-β1诱导的HepG2细胞中Smad2/3以及磷酸肌醇-3-激酶（PI3K）/Akt/mTOR信号通路的激活。总之，这些发现表明，水苏碱通过Smad2/3和PI3K/Akt/mTOR信号通路防止TGF-β1诱导的HCC细胞发生EMT。因此，水苏碱可能是治疗HCC的一种潜在治疗药物。
