Inhibitory Effect and Mechanism of 1,2,3,4,6‐O‐Pentagalloylglucose on Subcutaneous Xenograft of Gastric Cancer in Mice

Objective: 1,2,3,4,6‐O‐Pentagalloylglucose (PGG) has an inhibitory effect on various cancer types. This study aimed to investigate the impact and potential mechanism of PGG on gastric cancer. Methods: Network pharmacology predicted that PGG might inhibit gastric cancer through PI3K/AKT and MAPK signaling pathways. In vitro activity was studied by CCK‐8, plate cloning, apoptosis, cell cycle detection, mitochondrial membrane potential, and reactive oxygen species (ROS). In vivo activity was studied by H&E staining, TUNEL staining, qRT‐PCR, and western blot. Results: The results demonstrated that PGG inhibited the proliferation and induced apoptosis of mouse gastric cancer cell mouse forestomach carcinoma (MFC) in vitro, reduced mitochondrial membrane potential, and increased ROS content. In vivo, it can significantly inhibit tumor growth and induce apoptosis of tumor tissue, and it has no obvious toxicity to the body. On the PI3K/AKT and MAPK‐P38 pathways, the expression of BAX and CASP3 is upregulated and the expression of AKT and BCL‐2 is downregulated from the gene and protein levels. Conclusion: Comprehensive network pharmacology and experimental verification have demonstrated that PGG can play an antitumor role by regulating the PI3K/AKT and MAPK‐P38 signaling pathways to promote tumor apoptosis. PGG has been proven to be a potential therapeutic agent for gastric cancer.