Abstract: Objective To investigate the effect of HSP90 inhibitor on glycolysis and apoptosis in mouse hepatocarcinoma cells, and to explore its underlying mechanism. Methods Examine the level of lactate and ATP in mouse hepatoma cell line H22 treated with CORT, GR antagonist RU486 and HSP90 inhibitor 17-AAG; Evaluate the apoptosis level of H22 cells after CORT or various concentrations of 17-AAG treatment; H22 cells were treated with CORT, RU486 and 17-AAG respectively, and then the expression of GR and PI3K/Akt-related proteins was determined by Western blot. Results Compared with the control group, CORT promoted GR nuclear translocation, while inhibited after RU486 treatment. Compared with CORT treatment alone, CORT and 17-AAG co-treatment could weaken the promotion of GR nuclear translocation by CORT(P＜0.05); The level of lactate and ATP was increased significantly after CORT treatment (P＜0.05). After co-treatment with 17-AAG, this effect was inhibited (P＜0.05).And the level of lactate and ATP was decreased by 24% and 17% respectively; Compared with the control group, 17-AAG could significantly increase the total apoptosis rate of H22 cells in a dose-dependent manner(P＜0.05); Compared with the control group, the protein expression of pAkt increased after CORT treatment, while decreased significantly after co-treatment with 17-AAG (P＜0.05). Conclusions HSP90 inhibitor 17-AAG can inhibit GR nuclear translocation, thereby inhibit glycolysis and promote apoptosis of hepatocarcinoma cells, which is potentially regulated by PI3K/Akt pathway.

Key words: hepatocellular carcinoma, HSP90 inhibitor, glycolysis