@ARTICLE{10.3389/fphar.2022.851554, AUTHOR={Yang, Hongxing and Guo, Qiuyan and Wu, Jianbin and Zhong, Lixia and Sun, Lingling and Liu, Wei and Wang, Jigang and 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={13}, YEAR={2022}, URL={https://www.frontiersin.org/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 cases, calls for better therapy. Yi-Fei-San-Jie-pill (YFSJ), a well-applicated traditional Chinese medicine formula, was reported to be effective in the treatment of NSCLC. However, its anti-tumor mechanism still needs to be fully elucidated. Herein, a reliable preclinical orthotopic but not subcutaneous model of NSCLC in mice was established to evaluate the anti-cancer properties and further validate the mechanisms of YFSJ. A bioinformatic analysis was executed to identify the potential targets and key pathways of YFSJ on NSCLC. In detail, the anti-tumor effect of YFSJ and the autophagy inhibitor 3-MA was evaluated according to the tumor fluorescence value and comparison of different groups’ survival times. As a result, YFSJ markedly decreased tumor size and prolonged survival time in contrast with those in the orthotopic model group (p < 0.05), and it also significantly regulated the protein expression levels of apoptosis- and autophagy-related proteins. In conclusion, this study provides convincing evidence that YFSJ could inhibit the growth of tumors and prolong the survival time of tumor-bearing mice based on the NSCLC orthotopic model, and its anti-tumor effect was closely associated with the promotion of apoptosis and interference of autophagy coupled with regulation of immune infiltration.} }