Objective:To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula(FZKA)on tumor microenvironment(TME).Methods:CIBERSORTx was used for analysis of TME.Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas(TCGA)was employed to identify the differential expression genes(DEGs)between tumor and paracancerous tissues in lung adenocarcinoma(LUAD)from TCGA-LUAD.Additionally,DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression.The core targets of FZKA were analyzed in lung adenocarcinoma TME.Protein-protein interaction database was employed to predict down-stream of target.Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549,H1299 and PC9 cell lines.Results:The active and resting mast cells were significantly associated with prognosis of LUAD(P＜0.05).Of the targets,CCNA2 as an important target of FZKA(hazard ratio=1.41,95％confidential interval:1.01-2.01,P＜0.05)was a prognostic target and significantly associated with mast cells.CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state.BCL1L2,ACTL6A and ITGAV were down-stream of CCNA2,which were validated by qRT-PCR in A549 cell.Conclusion:FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.

TIAN Yun-ling;FU Song-bo;LI Bo;YUAN Ling-yan;BING Zhi-tong

Department of Endocrinology and Metabolism,the First Hospital of Lanzhou University,Lanzhou,730000,China;Evidence Based Medicine Center,School of Basic Medical Science of Lanzhou University,Lanzhou,730000,China;Department of Computational Physics,Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou,730000,China;School of Nuclear Science and Technology,University of Chinese Academy of Sciences,Beijing,100049,China

中国结合医学杂志（英文版）

[1]TIAN Yun-ling;FU Song-bo;LI Bo;YUAN Ling-yan;BING Zhi-tong-.Mechanism of Fuzheng Kang'ai Formula Regulating Tumor Microenvironment in Non-Small Cell Lung Cancer)[J].中国结合医学杂志（英文版）,2022(05):425-433

FZKA,paracancerous,BCL1L2

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