Aim To investigate the effect of bruceine A on apoptosis and invasion of non-small cell lung cancer(NSCLC)cells and to explore its possible molecular mechanism.Methods CCK-8 and cell colony assay were used to detect the effect of bruceine A on prolifer-ation and clone formation ability of NSCLC cells.3D matrigel drop invasion assay and flow cytometry were used to detect cell invasion ability and apoptosis rate.Western blot was used to detect expressions of epitheli-al-mesenchymal transition(EMT)key proteins and ap-optosis key proteins.The anti-tumor effect of bruceine A was detected on A549 xenograft mice in vivo.Online databases,molecular docking methods and drug affinity responsive target stability(DARTS)were used to pre-dict and screen the potential binding targets of bruceine A.Results Bruceine A significantly inhibited the proliferation and colony formation of NSCLC cells.Bruceine A significantly induced the apoptosis in NSCLC cells and inhibited cell invasion ability,signifi-cantly up-regulated the protein expressions of c-caspase3,c-PARP,Bax and E-cadherin,and signifi-cantly down-regulated the protein expressions of Bcl-2,N-cadherin,Vimentin and Snail(P＜0.05).In the tumor-bearing mouse models,bruceine A significantly decreased the tumor volume and tumor weight(P＜0.05).Target prediction,molecular docking and Western blot analysis of DARTS sample revealed that bruceine A could increase the stabilization of HSP90α.Conclusions Bruceine A reduces the EMT levels and induces apoptosis in NSCLC cells through the EMT signaling axis.Bruceine A may exert its anti-cancer effect by binding to HSP90α.

Coptidis Rhizoma-Evodia Fructus is a classic herb pair in traditional Chinese medicine prescriptions, the famous prescription is called Zuojinwan, which comes from Danxi Xinfa, is composed of Coptidis Rhizoma-Evodia Fructus (6∶1). In this formula, Coptidis Rhizoma has the effect of clearing heat and drying diuresis, purging fire to remove toxin and clearing heart. Evodia Fructus has the effects of expelling cold and alleviating pain, checking upward adverse flow of Qi tostop vomiting, and assisting yang to stop diarrhea. Coptidis Rhizoma has the properties of bitter and cold, and Evodia Fructus has the properties of pungent and calidus. Pungent drugs have divergent effects, and bitter drugs have sedimentation effect, when used in combination, they can clear the liver and purge fire, calm the adverse-rising energy and stop vomiting. On the basis of Zuojinwan, Coptidis Rhizoma-Evodia Fructus medicine has derived different compatibility ratios. Different ratios are different in terms of efficacy, usage, clinical application. Although with the application of modern analytical instruments and the development of molecular pharmacology theory, the chemical constituents and Pharmacological effects of Coptidis Rhizoma and Evodia Fructus have been fully studied, as to the principle of compatibility, and the study of pharmacological effects and chemical constituents after the compatibility of the two drugs in different proportions, there is still no comprehensive system summary. This article makes a systematic and comprehensive explanation of Coptidis Rhizoma-Evodia Fructus from the aspects of famous literature, chemical composition, pharmacological effects and clinical applicationthrough querying literature and ancient books. In order to make this herb pair more standardized, and provide reference materials for further research and development for this herb pair.