Flavonoid Benzimidazole Compound FB-15 Inhibits Proliferation Of Gastric Cancer Cells By Down-regulateing HIF-1?-induced Glycolysis

OBJECTIVE: To study the inhibitory effect of flavonoid benzimidazole compound FB-15 on the proliferation of gastric cancer cells MGC803 and HGC27,and to explore the molecular mechanism of its inhibitory effect on the proliferation of gastric cancer cells,so as to provide theoretical basis for better treatment of gastric cancer.Methods: CCK-8 assay was utilized to detect the effect of FB-15 on the activity of gastric cancer cells.The inhibitory effect of FB-15 detected by EDUmethod on the proliferation of gastric cancer cells;Hoechst staining was utilized to detect the effect of FB-15 on apoptosis of gastric cancer cells.Lactic acid kit was used to detect the inhibitory effect of FB-15 on lactic acid production in gastric cancer cells.Glucose kit was used to detect the inhibitory effect of FB-15 on glucose uptake in gastric cancer cells.ATP kit was used to detect the inhibitory effect of FB-15 on ATP generation in gastric cancer cells.Western Blot was used to detect the activity and expression of HIF-1? under hypoxia,and the expression of FB-15 on HIF-1? and Warburg-related enzymes(HK?,PKM2,PFKP)was detected.qRT-PCR assay was used to detect the expression of HIF-1? mRNA under hypoxia,and the expression of FB-15 on HIF-1? mRNA,HK? mRNA,PKM2 mRNA and PFKP mRNA.Results:1.FB-15 can significantly reduce the activity of MGC803/HGC27 cells in gastric cancer cells.2.FB-15 can significantly inhibit the proliferation of gastric cancer cells and promote the apoptosis of gastric cancer cells.3.FB-15 can inhibit the production of lactic acid in gastric cancer cells,decrease the consumption of glucose,down-regulate the generation of ATP in gastric cancer cells,and induce the apoptosis of gastric cancer cells.4.Under the condition of oxygen,the expression of HIF-1? increased significantly,FB-15 can inhibit HIF-1? expression,at the same time,the HK?,PKM2 and PFKP protein expression is cut down.5.qRT-PCR results showed that FB-15 significantly inhibited the expression of HIF-1? mRNA.At the same time,the HK? mRNA,PKM2 mRNA and PFKP mRNA expression cut down.Conclusion:HIF-1? can induce glycolysis in gastric cancer cells.FB-15 down-regulates HIF-1?-induced glycolysis and inhibits gastric cancer cell proliferation.