Endogenously synthesized n-3 fatty acids in fat-1 transgenic mice prevent melanoma progression by increasing E-cadherin expression and inhibiting β-catenin signaling

Yin,Xuan; Yu,Xiong‑Wei; Zhu,Pan; Zhang,Yuan‑Ming; Zhang,Xiao‑Hong; Wang,Feng; Zhang,Jin‑Jie; Yan,Wang; Xi,Yang; Wan,Jian‑Bo; Kang,Jing‑Xuan; Zou,Zu‑Quan; Bu,Shi‑Zhong

doi:10.3892/mmr.2016.5639

Endogenously synthesized n-3 fatty acids in fat-1 transgenic mice prevent melanoma progression by increasing E-cadherin expression and inhibiting β-catenin signaling

Authors:
- Xuan Yin
- Xiong‑Wei Yu
- Pan Zhu
- Yuan‑Ming Zhang
- Xiao‑Hong Zhang
- Feng Wang
- Jin‑Jie Zhang
- Wang Yan
- Yang Xi
- Jian‑Bo Wan
- Jing‑Xuan Kang
- Zu‑Quan Zou
- Shi‑Zhong Bu
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Affiliations: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Clinical Laboratory, Lihuili Hospital, Ningbo, Zhejiang 315040, P.R. China, Maritime Faculty, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Neurosurgery Department, Second Hospital of Ningbo, Ningbo, Zhejiang 315010, P.R. China, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR 519000, P.R. China, Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Published online on: August 18, 2016 https://doi.org/10.3892/mmr.2016.5639
Pages: 3476-3484

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Abstract

Malignant melanoma is the most lethal form of skin cancer. Although preclinical studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are beneficial for prevention of melanoma, the molecular mechanisms underlying the protective effects of n‑3 PUFAs on melanoma remain largely unknown. In the present study, endogenously increased levels of n-3 PUFAs in the tumor tissues of omega‑3 fatty acid desaturase (fat‑1) transgenic mice was associated with a reduction in the growth rate of melanoma xenografts. This reduction in tumor growth in fat‑1 mice compared with wild‑type controls may have been associated, in part, to the: i) Increased expression of E‑cadherin and the reduced expression of its transcriptional repressors, the zinc finger E‑box binding homeobox 1 and snail family transcriptional repressor 1; ii) significant repression of the epidermal growth factor receptor/Akt/β‑catenin signaling pathway; and iii) formation of significant levels of n‑3 PUFA‑derived lipid mediators, particularly resolvin D2 and E1, maresin 1 and 15‑hydroxyeicosapentaenoic acid. In addition, vitamin E administration counteracted n‑3 PUFA‑induced lipid peroxidation and enhanced the antitumor effect of n‑3 PUFAs, which suggests that the protective role of n‑3 PUFAs against melanoma is not mediated by n‑3 PUFAs‑induced lipid peroxidation. These results highlight a potential role of n‑3 PUFAs supplementation for the chemoprevention of melanoma in high‑risk individuals, and as a putative adjuvant agent in the treatment of malignant melanoma.

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