Fig. 6: LXR623 and SR9243 have no killing effect on normal renal tubular epithelial cells.

a Schematic diagram showing that non-malignant cells primarily support energy metabolism through the TCA; however, ccRCC cells primarily provide FAs for cell proliferation through the Warburg effect. b CCK8 assays were used to detect the viability of HK2 cells at different doses of SR9243 for 48, 72 and 96 h. c Analysis of mRNA expression differences in the SREBP-1c, FASN and SCD1 and the HMGCS1, HMGCR and DHCR24 between ccRCC and adjacent tissues in the TCGA database⁶⁵. d Immunoblot assay: proteins were extracted from HK2, 786-0 and ACHN cells. The protein levels of SREBP-1c, FASN, SCD1, HMGCR, SRB1 and LDLR were analysed via immunoblotting. e CCK8 assays were used to detect the viability of HK2 cells at different doses of SR9243 for 48, 72 and 96 h. f TCGA database analysis of the cholesterol influx genes SRB1 and LDLR in ccRCC and adjacent tissues⁶⁵. g, h HMGCR and SRB1 expression in a ccRCC tissue microarray; scale bars: 100 μm and 20 μm. The data are shown as the mean ± S.E.M. i Schematic showing that non-malignant cells have intact cholesterol compensatory mechanisms, whereas ccRCC cells are sensitive to exogenous LXR agonists due to a lack of endogenous LXR agonist oxysterols. j TCGA database analysis of the oxysterol synthesis genes CH25H and CYP11A1 and the oxysterol degradation gene HSD3B7⁶⁵