Abstract
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 Astragalus membranaceus, Polygonatum sibiricum, Atractylodes macrocephala, Cornus officinalis, Paris polyphylla, and Polistes olivaceous, etc. 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 G2/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.
Highlights
Lung cancer has the highest morbidity and mortality worldwide [1]
Major lung cancer types include small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter being further divided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, accounting for 85 to 90% of all lung cancers [2]
Collection of Target Points A total of 1,701 potential targets of traditional Chinese medicine (TCM) components were obtained after the prediction and screening by Seaware reverse target searching and Swiss Target Prediction database
Summary
Lung cancer has the highest morbidity and mortality worldwide [1]. Major lung cancer types include small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter being further divided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, accounting for 85 to 90% of all lung cancers [2]. Common therapies for lung cancer include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy [4]. Adverse effects such as mucositis, neurotoxicity, and extravasation are often caused by chemotherapy and radiotherapy. In China, traditional Chinese medicines (TCMs) are commonly prescribed as an adjuvant therapy to conventional cancer treatments to reduce such adverse reactions to radiotherapy and chemotherapy and improve the efficacy of treatment, improving the quality of life of patients and prolonging their survival. Various mechanisms of TCM have been proposed [5] with published evidence that TCM can improve general symptoms and even prolong the survival of cancer patients [6]. In many instances, TCM is prescribed without objective evidence of mechanism
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