title: Endogenously synthesized n-3 fatty acids in fat-1 transgenic mice prevent melanoma progression by increasing E-cadherin expression and inhibiting β-catenin signaling.
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.
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Xuan
authors: X
authors: Yin
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Xiong-Wei
authors: XW
authors: Yu
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Pan
authors: P
authors: Zhu
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Yuan-Ming
authors: YM
authors: Zhang
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Xiao-Hong
authors: XH
authors: Zhang
authors: Clinical Laboratory, Lihuili Hospital, Ningbo, Zhejiang 315040, P.R. China.
authors: Feng
authors: F
authors: Wang
authors: Maritime Faculty, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Jin-Jie
authors: JJ
authors: Zhang
authors: Neurosurgery Department, Second Hospital of Ningbo, Ningbo, Zhejiang 315010, P.R. China.
authors: Wang
authors: W
authors: Yan
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Yang
authors: Y
authors: Xi
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, SAR 519000, P.R. China.
authors: Jian-Bo
authors: JB
authors: Wan
authors: Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors: Jing-Xuan
authors: JX
authors: Kang
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Zu-Quan
authors: ZQ
authors: Zou
authors: Medical School, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
authors: Shi-Zhong
authors: SZ
authors: Bu
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D044943:Fatty Acid Desaturases / Q000235:genetics*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D015525:Fatty Acids, Omega-3; D051176:beta Catenin; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases