Effects of squalene on expression of LDLR in HepG2 cells and its mechanism / 中国药理学通报

ABSTRACT

Aim To investigate the effect of squalene on LDLR expression in HepG2 cells and its mechanism of down-regulated cholesterol. Methods The prolifer-ation of HepG2 cells exposed to squalene at different concentrations was measured by MTT assay. The effect of squalene on the expression of LDLR in HepG2 cells was measured by flow cytometry and fluorescence mi-croscopy. The effect of different concentrations of squa-lene on the interaction between SCAP and Insig2, two key protein molecules of SREBP pathway, was assayed by FRET technology. Results MTT results showed that squalene had inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner. Flow cy-tometry and fluorescence microscopy results showed that squalene enhanced LDLR expression in HepG2 cells compared with the control group. The results of FRET technology revealed that compared with model control group, the YFP fluorescence value in Squalene group dramatically declined, and the YFP fluorescence value of each drug group decreased with the range of 5~25 μmol·L-1 squalene concentration. Conclusions Squalene may promote the expression of LDLR in HepG2 cells through inhibiting the interaction between SCAP and Insig2 proteins in SREBP pathway, which may confirm that squalene is a potential novel drug for the down-regulation of cholesterol level.