Ze-Qi decoction inhibits non-small cell lung cancer growth and metastasis by modulating the PI3K/Akt/p53 signaling pathway

BACKGROUND: The Ze-Qi decoction (ZQD) is a traditional Chinese herbal formula commonly applied to treat lung cancer in China. This study aimed to assess the effective ingredients and molecular mechanisms of ZQD in treating non-small cell lung cancer (NSCLC) based on network pharmacology combined with experimental validation. METHODS: Network pharmacology, bioinformatics, and molecular docking analyses were conducted to explore the mechanism of ZQD for treating NSCLC, which was further confirmed by animal experiments. RESULTS: In total, 117 bioactive ingredients and 499 target proteins of ZQD were identified. Network pharmacology revealed 7 core active ingredients and 74 core target proteins. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the PI3K/Akt and p53 signaling pathways may be crucial in NSCLC treatment. Molecular docking analysis revealed that the seven crucial bioactive ingredients complexed with PI3K, Akt, and p53. The animal experiment results validated that ZQD treatment promoted cell apoptosis and cell cycle arrest, thereby inhibiting NSCLC growth and metastasis. Furthermore, ZQD treatment caused a significant increase in p53 and Bax, while leading to a distinct reduction in p-PI3K (Tyr317), p-Akt (Ser473), VEGFA, CD31, MMP2, MMP9, Bcl2, and CDK2. CONCLUSIONS: ZQD inhibited the growth and metastasis of NSCLC subcutaneous tumors in C57BL/6J mice via the PI3K/Akt/p53 signaling pathway.