Figure 7.

A proposed model for the remodeling of cholesterol metabolism in the transition from a chemosensitive to a chemoresistant phenotype in human ovarian cancer cells. Drug-sensitive cells show significant activation of the cholesterol biosynthetic pathway and transport of cholesterol through the Golgi apparatus, while uptake of exogenous cholesterol through the LDLR is limited. Drug resistant cells, on the opposite, show reduced levels of FDPS and OSC along the biosynthetic pathway and increased LDL uptake. The inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the biosynthetic pathway, by statins induces drug resistance, whereas the reduction of LDL recycling and lipid absorption through extracellular lipid withdrawal or LIPG knockdown sensitizes cells to drug-induced apoptosis. Enzymes whose expression has been analyzed in this work are in bold red. IPP = isopentenyl pyrophosphate; FPP = farnesyl pyrophosphate; TCA = tricarboxylic acid. This image was created using images from Servier Medical Art under Creative Commons Attribution 3.0 Unported License (https://smart.servier.com).