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Uncovering the anticancer mechanism of petroleum extracts of Farfarae Flos against Lewis lung cancer by metabolomics and network pharmacology analysis
Authors:Shuting Yu  Jing Li  Wei Gao  Yongyan Wu  Xuemei Qin  Zhenyu Li
Affiliation:1. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi, People's Republic of China

College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, Shanxi, People's Republic of China;2. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan, Hubei, People's Republic of China;3. Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Department of Otolaryngology Head & Neck Surgery, the First Hospital, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China;4. Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, Shanxi, People's Republic of China

Abstract:Lung cancer shows the highest incidence rate in the world. Thus, it has become increasingly important to find therapeutic drugs to treat lung cancer. Farfarae Flos (FF) has been used in traditional Chinese medicine to treat pulmonary diseases such as cough, bronchitis and asthmatic disorders. In this study, the anti-proliferation effects of petroleum extracts of FF (PEFF) on Lewis lung cancer cells and the corresponding mechanisms were studied using cell metabolomics. Fifteen differential metabolites in the cell extracts and the corresponding medium related to the anti-proliferation effect of PEFF were identified, which were probably involved in pyruvate metabolism and glycine, serine and threonine metabolism. For the cellular uptake compounds in PEFF, six metabolites derived from two prototype compounds were also tentatively identified by UHPLC-Q-Orbitrap high-resolution MS. Network pharmacology analysis demonstrated that the anti-proliferation mechanism of PEFF was also probably related to the target genes, including, Aurora-A, glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase P 1 (GSTP1), progesterone receptor and heme oxygenase-1 (HO-1), and further associated with the proteoglycans and PI3K/Akt signaling pathway. Cell metabolomics and network pharmacology analysis provided a holistic method to investigate the anti-proliferation mechanisms of PEFF. However, further studies were still needed to validate the potential target genes, pathways and active compounds in PEFF.
Keywords:cellular uptake compounds  Farfarae Flos  Lewis lung cancer cells  metabolomics  network pharmacology
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