AUTHOR=Yang Hongxing , Guo Qiuyan , Wu Jianbin , Zhong Lixia , Sun Lingling , Liu Wei , Wang Jigang , Lin Lizhu TITLE=Deciphering the Effects and Mechanisms of Yi-Fei-San-Jie-pill on Non-Small Cell Lung Cancer With Integrating Network Target Analysis and Experimental Validation JOURNAL=Frontiers in Pharmacology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.851554 DOI=10.3389/fphar.2022.851554 ISSN=1663-9812 ABSTRACT=Non-Small Cell Lung Cancer (NSCLC), which accounts for 85% of lung cancer, calls for better therapy. Yi-Fei-San-Jie-Pill, a well applicated traditional Chinese medicine formula, was reported to be effective in the treatment of NSCLC. Whereas, it’s anti-tumor mechanism still need to be fully elucidated. Herein, a reliable preclinical orthotopic but not subcutaneous model of NSCLC in mice was established to evaluate the anti-cancer characters and further validate the mechanisms of Yi-Fei-San-Jie-Pill. Bioinformatic analysis was executed to identify the potential targets and key pathways of Yi-Fei-San-Jie-Pill on NSCLC. In detail, the anti-tumor effect of Yi-Fei-San-Jie-Pill and the autophagy inhibitor 3-MA was evaluated according to the tumor fluorescence value and comparation of different groups’ survival time. As a result, Yi-Fei-San-Jie-Pill, markedly decreased tumor size and prolonged survival time in contrast with those in model group (P<0.05), also regulated the protein expression levels of apoptosis- and autophagy-related proteins dramatically. In conclusion, this study provides convincing evidence that Yi-Fei-San-Jie-Pill could inhibit the growth of tumor and prolong the survival time of tumor-bearing mice based on NSCLC orthotopic model and its anti-tumor effect was closely associated with the promotion of apoptosis and interfering of autophagy coupled with regulation of immune infiltration.