The fatty acid synthase inhibitor orlistat reduces experimental metastases and angiogenesis in B16-F10 melanomas
British Journal of Cancer, 08/17/2012
Seguin F et al. – FASN inhibitors reduce metastasis and tumour-induced angiogenesis in experimental melanomas, and differentially modulate VEGFA expression in B16-F10 cells.Methods
- The lung colonisation assay and cutaneous melanomas were performed by the inoculation of mouse melanoma B16-F10 cells in C57BL6 mice.
- Blood vessel endothelial cells (RAEC and HUVEC) were applied to determine cell proliferation, apoptosis, and the formation of capillary-like structures.
- Vascular endothelial growth factor A (VEGFA) expression was evaluated by quantitative RT–PCR and ELISA in B16-F10, human melanoma (SK-MEL-25), and human oral squamous carcinoma (SCC-9) cells.
- Conditioned media from these cancer cell lines were used to study the effects of FASN inhibitors on endothelial cells.
- B16-F10 melanoma-induced metastases and angiogenesis were significantly reduced in orlistat-treated mice.
- Fatty acid synthase inhibitors reduced the viability, proliferation, and the formation of capillary-like structures by RAEC cells, as well as the tumour cell-mediated formation of HUVEC capillary-like structures.
- Cerulenin and orlistat stimulated the production of total VEGFA in B16-F10, SK-MEL-25, and SCC-9 cells.
- Both drugs also enhanced VEGFA121, 165, 189, and 165b in SK-MEL-25 and SCC-9 cells.