Virtual screening to investigate the potential targets and mechanisms of action of "Astragalus-Ligustrum" drug pair in the treatment of non-small cell lung cancer

Abstract

Abstract Astragalus membranaceus and Ligustrum lucidum are the common main components in Chinese patent medicine preparations which have been widely used in combination chemotherapy for tumor treatment. However, the specific mechanism of their anti-cancer effect has not been fully elucidated, and the traditional monomer research mode can hardly reflect the feature of Chinese medicine in treating diseases. In this study, virtual screening was used to explore the mechanism of “Astragalus-Ligustrum” drug pair in the treatment of non-small cell lung cancer (NSCLC). 28 active ingredients and 180 active ingredient targets were screened out from the drug pair by network pharmacology. Among them, 10 components, including quercetin and kaempferol, are the main active ingredients in the drug pair, whose mechanism of anti-NSCLC is to modulate the pathways of PI3K-Akt, PD-1/PD-L1, and T-cell receptor, and by affecting the biological processes such as protein phosphorylation and cellular response to growth factor stimulation. Then molecular docking and molecular dynamics validation showed that the complexes can bind tightly to target proteins in the active pocket through van der Waals, hydrophobic and π-bonds. The binding of PD-L1 to the main active ingredient may be one of the important mechanisms of its anti-NSCLC action. At last, Survival curve analysis and immunohistochemical analysis showed TP53, PIK3R1, PD-L1 and other target genes above had significant differences in expression in lung cancer patients. In conclusion, this study explored the active components of "Astragalus-Ligustrum" drug pair in anti-NSCLC and elucidated the mechanism of its action.