Pharmacological inhibition of lipid import and transport proteins in ovarian cancer

Ovarian cancer (OC) is still the most fatal gynecological cancer due to late diagnosis when peritoneal metastasis has already occurred. OC progression requires lipid nutrients that are either synthesized endogenously in the cancer cells or imported from the surrounding host tissue. Accordingly, blockade of lipid synthesis has been shown to be a powerful strategy against OC. However, direct evidence of the role of lipid import and transport for OC growth is still largely missing. Therefore, we exposed OC cells to inhibitors of lipid uptake and transport proteins, which are typically overexpressed in OC. Our data reveal that pharmacological inhibition of these lipid handling proteins caused drug-specific, dose- and time-dependent decline of lipid-uptake, which was associated with cell growth reduction, cell cycle arrest and apoptosis indicating that OC cells are exquisitely sensitive to lipid deficiency. This dependency provides the rationale for the development of novel lipid-antimetabolic strategies against OC. Overall design: RNA-seq experiments; gene expression differences between ovarian cancer cell lines treated with BMS309403, HTS01037, NAV2729, SB-FI-26 or sulfosuccinimidyl-oleate (SSO) were analysed in biological triplicates.