Objective: To observe the anti-glycolysis effect of toosendanin (TSN) in gastric cancer cells and its effect on the regulatory factors of glucose metabolism related Sirtuin-3 (SIRT3), signal transducer and activator of transcription 3 (STAT3) and hypoxia inducible factor-1α(HIF-1α)， and to explore the potential mechanism of anti-glycolysis effect of TSN in gastric cancer cells.Methods: The expression of SIRT3, STAT3 and HIF-1α in 31 paraffin gastric cancer samples were detected by immunohistochemistry, and the correlation between SIRT3 and the expression level of STAT3 and HIF-1α were analyzed. The gastric cancer cell lines AGS and HGC-27 were treated with 100 nmol/L TSN, 250 nmol/L TSN or equivoluminal solvent for 24 hours. The effect of TSN on glucose uptake and lactate production in gastric cancer cells were detected by using glucose metabolism kits. The mRNA expression level of key glycolysis-related genes were tested by real-time quantitative PCR(qRT-PCR). The transcriptional regulation of SIRT3 was analyzed by using the dual luciferase reporter system. Results:  The immunohistochemistry results showed that the expression of SIRT3 was negatively correlated with STAT3 and HIF-1α, and STAT3 was positively correlated with HIF-1α in gastric cancer tissue (all P<0.05). Compared with the control group, TSN significantly inhibited the glycolytic effect of gastric cancer cells and inhibited the ability of tumor cells to absorb glucose and secrete lactic acid (all P<0.05). After treating with TSN for 24 hours, the expression of key glycolytic enzymes glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA) in gastric cancer cells were significantly reduced (all P<0.05). The expression level of STAT3 and HIF-1α decreased after TSN treatment, while the expression level of SIRT3 increased. TSN could enhance the luciferase activity in the promoter region of SIRT3, while overexpression of STAT3 could partly weak the role of SIRT3 (all P<0.01). Conclusion: TSN could induce the transcriptional expression of SIRT3 by inhibiting STAT3 expression, thereby inhibiting the expression of HIF-1α, inhibiting the glycolytic effect of gastric cancer cells, and causing the transformation of the glucose metabolism of gastric cancer cells.

［Key words］gastric cancer; toosendanin; antitumor; glycolysis effect; HIF-1α