TO901317 inhibits the development of hepatocellular carcinoma by LXRα/Glut1 decreasing glycometabolism
Abstract
This study was conducted 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 expressions of liver X receptor (LXR)-α, glucose transporter (Glut)-1, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinase (MMP)-9 were analyzed from HCC public database (NCBI PubMed database). The result showed that LXRα was downregulated, whereas Glut1, PCNA, and MMP9 were upregulated 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 in nude mice to establish the 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 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. With the increase of TO901317 concentration, the cellular glucose concentration and ATP level were gradually decreased. Western blot results showed TO901317 could u...Continue Reading
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