Endogenously synthesized n-3 polyunsaturated fatty acids in fat-1 transgenic mice suppress B16F10 melanoma lung metastasis by impairing mesenchymal to epithelial transition

• Main Authors: Pan Zhu, Yuan-Ming Zhang, Xuan Yin, Xiao-Hong Zhang, Feng Wang, Jin-Jie Zhang, Wang Yan, Yang Xi, Jian-Bo Wan, Jing-Xuan Kang, Zu-Quan Zou, Shi-Zhong Bu
• Format: Article
• Language: English
• Published: Elsevier 2016-12-01
• Series: Journal of Functional Foods
• Subjects: Fat-1; n-3 polyunsaturated fatty acids; Mesenchymal to epithelial transition; Lipid mediators; IL-1β; Melanoma
• Online Access: http://www.sciencedirect.com/science/article/pii/S175646461630319X

Malignant melanoma is an aggressive cancer of neuroectodermal origin. The mechanisms of n-3 polyunsaturated fatty acids (PUFAs) against melanoma metastasis are not clear. Here fat-1 and wild type (WT) mice were injected with B16F10 melanoma cells via the tail vein to establish lung metastasis model. Endogenous n-3 PUFAs were associated with a reduction in grossly visible pulmonary metastases and outgrowth through inhibition of mesenchymal to epithelial transition (MET), which was characterized by decreased expression of epithelial markers E-cadherin and ZO-1, and increased expression of mesenchymal marker vimentin in tumour tissues from fat-1 mice compared with WT controls. In addition, n-3 PUFA-mediated inhibition of MET may have been associated, in part, with the: (i) formation of n-3 PUFA-derived lipid mediators and (ii) decreased expression of mature IL-1β and p-NF-κB, and enhanced expression of superoxide dismutase-1. These results suggest that n-3 PUFAs exert their antitumourigenic activities, in part, via their anti-inflammatory properties.