TO901317 Inhibits The Progress Of Liver Cancer By Liver X Receptor α Down-regulating The Glucose Metabolism

OBJECTIVE To observe the effect and possible mechanism of TO901317 on liver carcinoma in vivo and in vitro to provide a kind of new basis for the targeted therapy of this disease.METHODS 1 Liver cancer cells were cultivated in vitro and axillary injected into nude mice to establish xenograft model.After the tumor was observed obviously,the nude mice were treated with TO901317(25 mg/kg,intraperitoneal injection every other day).Nude mice were executed after about four weeks.The tumor was separated and weighted.The protein expression of LXRα,Glut1 and MMP9 was detected by western blot and the glucose level was detected by glucose assay kit.2 Effect of different concentration of TO901317(0 μM,8μM,16 μM,24 μM,32 μM)on the cell proliferation of liver carcinoma was deteced by MTT assay.The effect of TO901317 on the cell invasion and migration was detected by transwell and wound healing analysis.The glucose concentration was investigated by using glucose and ATP assay kit.At the same time,the protein expression of LXRα,Glut1 and MMP9 was detected by western blot.3 After LXRα expression silenced by LXRα siRNA,the effect of TO901317 on glucose concentration,invasion,migration,and the expression of LXRα,Glut1 and MMP9 were detected.RESULTS 1 After treated with TO901317,the tumor of xenograft tended to be slower and smaller than non-treatment group.Besides,LXRα expression was up-regulated but the expression of Glut1 and MMP9 were down-regulted.Furthermore,the glucose content oftreatment group was reduced.2 MTT assay showed that TO901317 could inhibit the cell proliferation of liver carcinoma in a dose-dependent manner.With the concentration of TO901317 increasing,the cellular glucose concentration and ATP level were decreased.Western blot detection showed that TO901317 could up-regulate LXRα expression but down-regulate MMP9 and Glut1 expression.Transwell and wound healing analysis confirmed that with the dose of TO901317 increasing,the cell invasion and migration were both dcreased.3 LXRα siRNA could relieve the suppression effect of TO901317 on the cell invasion and migration and the expression of LXRα,MMP9 and Glut1.The glucose concentration was also increased.CONCLUSIONS TO901317 could repress the progress of liver cancer cells by reducing the glucose concentration,up-regulating LXRαexpression but down-regulating the expression of Glut1 and MMP9.