School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
J Cancer Res Clin Oncol. 2023 Feb;149(2):553-566. doi: 10.1007/s00432-022-04280-y. Epub 2022 Aug 19.
The compounds derived from Traditional Chinese Medicines have shown various pharmacological activities with unique advantages, especially in the aspect of antitumor. Neferine (Nef), a natural compound, extracted from green seed embryos of Lotus (Nelumbo nucifera Gaertn.) also exerts antitumor effects on cancers. In this study, the effects and mechanisms of Nef on epithelial-to-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC) were evaluated. The results showed that Nef had the antitumor effects in vivo and in vitro. Nef significantly suppressed cell viability and induced apoptosis in NSCLC cells, with elevated reactive oxygen species and reduced BCL2/BAX ratio. Nef was also demonstrated to inhibit the invasion, metastasis and EMT process of NSCLC cells, and attenuate EMT-related changes of E-cadherin, N-cadherin and Vimentin at both transcriptional and translational levels. Moreover, we concluded that the inhibitory effects of Nef on EMT was achieved by targeting Rho-associated protein kinase 1, a protein mediating the process of EMT in various cancers. These results showed that Nef had a significant antitumor effect on NSCLC cells by inducing apoptosis and blocking EMT, providing the therapeutical prospect on NSCLC treatment.
从中药中提取的化合物具有多种药理活性,具有独特的优势,特别是在抗肿瘤方面。荷叶碱(Nef)是从莲(Nelumbo nucifera Gaertn.)绿种子胚中提取的天然化合物,对癌症也具有抗肿瘤作用。本研究评价了 Nef 对非小细胞肺癌(NSCLC)上皮间质转化(EMT)过程的作用及其机制。结果表明,Nef 具有体内和体外抗肿瘤作用。Nef 显著抑制 NSCLC 细胞的活力并诱导其凋亡,同时增加活性氧并降低 BCL2/BAX 比值。Nef 还能抑制 NSCLC 细胞的侵袭、转移和 EMT 过程,并在转录和翻译水平上减弱 EMT 相关的 E-钙粘蛋白、N-钙粘蛋白和波形蛋白的变化。此外,我们得出结论,Nef 通过靶向 Rho 相关蛋白激酶 1(一种在多种癌症中介导 EMT 过程的蛋白)来抑制 EMT。这些结果表明,Nef 通过诱导细胞凋亡和阻断 EMT 对 NSCLC 细胞具有显著的抗肿瘤作用,为 NSCLC 的治疗提供了治疗前景。