Department of Oral Diagnosis, School of Dentistry of Piracicaba, University of Campinas, Avenida Limeira 901, CP 52, Areão, Piracicaba, CEP 13414-018, SP, Brazil.
Br J Cancer. 2012 Sep 4;107(6):977-87. doi: 10.1038/bjc.2012.355. Epub 2012 Aug 14.
Fatty acid synthase (FASN) is overexpressed and associated with poor prognosis in several human cancers. Here, we investigate the effect of FASN inhibitors on the metastatic spread and angiogenesis in experimental melanomas and cultured melanoma cells.
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 VEGFA(121), (165), (189,) and (165b) in SK-MEL-25 and SCC-9 cells.
FASN inhibitors reduce metastasis and tumour-induced angiogenesis in experimental melanomas, and differentially modulate VEGFA expression in B16-F10 cells.
脂肪酸合酶（FASN）在多种人类癌症中过度表达，并与不良预后相关。在这里，我们研究了 FASN 抑制剂对实验性黑色素瘤和培养的黑色素瘤细胞转移和血管生成的影响。
通过将小鼠黑色素瘤 B16-F10 细胞接种到 C57BL6 小鼠中进行肺定植实验和皮肤黑色素瘤实验。应用血管内皮细胞（RAEC 和 HUVEC）来确定细胞增殖、凋亡和毛细血管样结构的形成。通过定量 RT-PCR 和 ELISA 评估 B16-F10、人黑色素瘤（SK-MEL-25）和人口腔鳞状细胞癌（SCC-9）细胞中血管内皮生长因子 A（VEGFA）的表达。使用这些癌细胞系的条件培养基研究 FASN 抑制剂对内皮细胞的影响。
在奥利司他治疗的小鼠中，B16-F10 黑色素瘤诱导的转移和血管生成显著减少。脂肪酸合酶抑制剂降低了 RAEC 细胞的活力、增殖和毛细血管样结构的形成，以及肿瘤细胞介导的 HUVEC 毛细血管样结构的形成。 cerulenin 和奥利司他刺激了 B16-F10、SK-MEL-25 和 SCC-9 细胞中总 VEGFA 的产生。这两种药物还增强了 SK-MEL-25 和 SCC-9 细胞中 VEGFA(121)、(165)、(189)和(165b)的表达。
FASN 抑制剂可减少实验性黑色素瘤的转移和肿瘤诱导的血管生成，并在 B16-F10 细胞中差异调节 VEGFA 的表达。
