Ginkgolide B Inhibits EMT and Promotes Pyroptosis in Gastric Cancer via AKT/mTOR Pathway

Xinxing Lu,1,* Yan Zhang,1,* Ran Wang,2 Ziyu Li1 1Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ziyu Li, Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of China, Email [email protected]: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration of novel therapeutic agents to improve patient outcomes. This study elucidates the anti-cancer properties of Ginkgolide B (GGB), a diterpenoid lactone derived from Ginkgo biloba, in both in vitro and in vivo models of GC.Methods and Results: Using AGS and HGC-27 cell lines, we assessed GGB’s impact on cellular proliferation, colony formation, migration, invasion, apoptosis, and pyroptosis. GGB exhibited significant dose- and time-dependent inhibition of cell proliferation and colony formation, with no cytotoxicity observed in normal gastric epithelial cells. Furthermore, GGB markedly suppressed migration and invasion, and induced apoptosis and pyroptosis, as evidenced by increased Bax and GSDMD expression and decreased Bcl-2 levels. In vivo, GGB treatment significantly reduced tumor growth in a nude mouse xenograft model and modulated EMT markers, decreasing PCNA and N-cadherin levels while increasing E-cadherin expression. Mechanistically, GGB’s anti-cancer effects were mediated through the deactivation of the PI3K/AKT/mTOR signaling pathway.Conclusion: These findings underscore the potential of GGB as a promising therapeutic agent for GC, warranting further clinical evaluation.Keywords: gastric cancer, Ginkgolide B, EMT, pyroptosis, PI3K/AKT/mTOR