Zhu Li-Min, Shi Hai-Xia, Sugimoto Masahiro, Bandow Kenjiro, Sakagami Hiroshi, Amano Shigeru, Deng Hai-Bin, Ye Qing-Yu, Gai Yun, Xin Xiao-Li, Xu Zhen-Ye
Department of Oncology, LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Traditional Chinese Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2021 Jul 2;11:690878. doi: 10.3389/fonc.2021.690878. eCollection 2021.
Feiyanning formula (FYN) is a traditional Chinese medicine (TCM) prescription used for more than 20 years in the treatment of lung cancer. FYN is composed of , , , , , and , All of them have been proved to have anti-tumor effect. In this study, we used the TCM network pharmacological analysis to perform the collection of compound and disease target, the prediction of compound target and biological signal and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. It was found that the activation of mitochondrial pathway might be the molecular mechanism of the anti-lung cancer effect of FYN. The experimental results showed that FYN had an inhibitory effect on the growth of lung cancer cells in a dose-dependent and time-dependent manner. Moreover, FYN induced G/M cell cycle arrest and apoptotic cell death as early as 6 h after treatment. In addition, FYN significantly induced mitochondrial membrane depolarization and increased calreticulin expression. Metabolomics analysis showed the increase of ATP utilization (assessed by a significant increase of the AMP/ATP and ADP/ATP ratio, necessary for apoptosis induction) and decrease of polyamines (that reflects growth potential). Taken together, our study suggested that FYN induced apoptosis of lung adenocarcinoma cells by promoting metabolism and changing the mitochondrial membrane potential, further supporting the validity of network pharmacological prediction.
肺炎宁方（FYN）是一种在肺癌治疗中应用了20多年的中药方剂。FYN由[具体成分缺失]、[具体成分缺失]、[具体成分缺失]、[具体成分缺失]、[具体成分缺失]和[具体成分缺失]组成，所有这些成分均已被证明具有抗肿瘤作用。在本研究中，我们运用中药网络药理学分析进行化合物和疾病靶点的收集、化合物靶点及生物信号的预测以及京都基因与基因组百科全书（KEGG）通路富集分析。结果发现，线粒体途径的激活可能是FYN抗肺癌作用的分子机制。实验结果表明，FYN对肺癌细胞的生长具有剂量依赖性和时间依赖性抑制作用。此外，FYN早在处理后6小时就诱导G/M期细胞周期阻滞和凋亡性细胞死亡。另外，FYN显著诱导线粒体膜去极化并增加钙网蛋白表达。代谢组学分析显示ATP利用增加（通过凋亡诱导所必需的AMP/ATP和ADP/ATP比值显著升高来评估）以及多胺减少（反映生长潜力）。综上所述，我们的研究表明FYN通过促进代谢和改变线粒体膜电位诱导肺腺癌细胞凋亡，进一步支持了网络药理学预测的有效性。
