Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer

BackgroundFatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells’ increased demands for membrane, energy, and protein production.MethodsWe investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition’s impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and 18 F-fluoromethylcholine uptake measurement, respectively.ResultsRelative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold–100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin’s half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower 18 F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy.ConclusionsFASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.

• Publication year

  2015

• Venue

  Journal of Translational Medicine

• Publication date

  2015-05-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s12967-015-0511-3PMID 25947066PMCID 4504229
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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