Abstract: In view of the high morbidity and mortality of lung cancer, lung cancer was concerned and human non-small cell lung cancer A549 cells were used as the target in this study. Here, after screening 124 kinds of medicinal plants in A549 lung cancer cells and the determination of their anticancer orders, an efficient and novel compound formula of AEAMP9 was developed and its underlying molecular mechanism was investigated. AEAMP9 was prepared from the alcoholic extracts of six anticancer medicinal plants including Hedyotis diffusa Willd. (Bai Hua She She Cao), Phellodendron amurense Rupr. (Huang Bai), Glycyrrhiza uralensis Fisch. (Gan Cao), Platycladus orientalis (L.) Franco (Ce Bai Ye), Chrysanthemum indicum L. (Ye Ju Hua) and Notopterygium incisum Ting ex H. T. Chang (Qiang Huo). It can effectively inhibit the viability and clone formation of cancer cells, provoke apoptosis and block migration in A549 cells. Mechanistically, AEAMP9 significantly decreased the expressions of ABCG2, FoxM1, Vimentin, MMP14 and the ratio of Bcl-2/Bax, consequently promoted the activation of apoptosis associated genes including p53, caspase 3, caspase 8 and caspase 9. Network pharmacology and transcriptome RNA-seq revealed that many genes were significantly and differentially expressed in A549 cells after treatment with AEAMP9. TNF, IL-17 and other important signal pathways related to tumor, inflammation and apoptosis were closely regulated. EGR1, IL-6, ALK and VEGF may be the key regulatory targets for the interaction of AEAMP9 and lung adenocarcinoma. The components of quercetin, kaempferol and luteolin in AEAMP9 may play an important role in antitumor activity. Safely, AEAMP9 had no obvious toxic effects on SPF Kunming mice. Furthermore, AEAMP9 can significantly inhibit the tumor growth in mouse A549 xenograft models

Key words: AEAMP9, cell apoptosis, cancer, medicinal plant, network pharmacology