Cinnamaldehyde inhibits the progression of gastric cancer by regulating glycolysis through PTP1B/PI3K/AKT/mTOR signaling pathway.

Gastric cancer (GC) is a prevalent malignancy for which novel therapeutic approaches are urgently needed. Cinnamaldehyde (CA), a natural compound with anti-tumor potential, has an unclear mechanism of action in GC. This study aimed to investigate whether CA suppresses GC progression by modulating the PTP1B/PI3K/Akt/mTOR signaling pathway and its downstream glycolytic metabolism. The effects of CA on GC cell proliferation, migration, and invasion were evaluated through functional assays. Western blotting and metabolite detection were employed to analyze its impact on the PTP1B/PI3K/Akt/mTOR pathway and glycolysis. The critical role of PTP1B in mediating CA's effects was determined using lentivirus-mediated knockdown and overexpression. Finally, a nude mouse xenograft model was used to validate the anti-tumor efficacy of CA in vivo. In vitro, CA significantly inhibited the proliferation, migration, and invasion of GC cells, concurrently suppressing the activation of the PTP1B/PI3K/Akt/mTOR pathway and reducing glycolytic activity. PTP1B knockdown potentiated the anti-tumor and glycolytic-inhibitory effects of CA, whereas PTP1B overexpression partially reversed them. In vivo, CA markedly suppressed the growth of xenograft tumors. Collectively, these findings demonstrate that CA inhibits GC progression by targeting the PTP1B/PI3K/Akt/mTOR-glycolysis axis, revealing a novel mechanism and a potential therapeutic strategy.