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TO901317 inhibits the development of Hepatocellular Carcinoma by LXRα/Glut1 decreasing the glycometabolism.
American Journal of Physiology. Gastrointestinal and Liver Physiology 2019 Februrary 29
To observe the effect and possible mechanism of TO901317 in vivo and in vitro to provide a new basis for the targeted therapy of Hepatocellular carcinoma (HCC). The expression of LXRα, Glut1, PCNA and MMP9 were analyzed from the HCC public database. The result showed that LXRα was down-regulated, whereas Glut1, PCNA and MMP9 were up-regulated in human HCC compared with normal liver. Furthermore, LXRα mRNA was negatively correlated with Glut1 mRNA. At the same time, HCC cells were cultivated in vitro and axillary injected into nude mice to establish xenograft model. The xenograft in the TO901317 treated group was slower and smaller than the control group. The protein expression of LXRα, Glut1 and MMP9 could be detected by western blot and glucose level. As a result, TO901317 could inhibit the cell proliferation of HCC in a dose-dependent manner by MTT assay. With the increase of TO901317 concentration, the cellular glucose concentration and ATP level were gradually decreased. Western blot results showed TO901317 could up-regulate LXRα expression but down-regulate MMP9 and Glut1 expression. Transwell and wound healing analysis confirmed that with the increasing the concentration of TO901317, the cell invasion and migration were both decreased. LXRα siRNA could relieve the suppression effect of TO901317 on the cell invasion and migration and the expression of LXRα, Glut1 and MMP9. The glucose concentration was also raised. TO901317 could repress the progress of HCC cells by reducing the glucose concentration, up-regulating LXRα expression but down-regulating the expression of Glut1 and MMP9.
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