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Carcinogenesis Advance Access published online on January 20, 2005

Carcinogenesis, doi:10.1093/carcin/bgi019
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Oxford University Press
Received August 18, 2004
Revised January 1, 2005
Accepted January 8, 2005

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by down-regulation of cell adhesion/invasion-related genes

Shu-Hua Xia 1, Jingdong Wang 1, and Jing X. Kang 1*

1 Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114

* To whom correspondence should be addressed.
Jing X. Kang, E-mail: kang.jing{at}mgh.harvard.edu


   Abstract

Recent studies have shown opposing effects of n-6 and n-3 fatty acids on cancer development and suggest a role for the ratio of n-6 to n-3 fatty acids in cancer control. However, whether alteration in the n-6/n-3 fatty acid ratio of cancer cells affects their invasive potential has not been well investigated. We recently developed a genetic approach to modify the n-6/n-3 ratio by expression of the C. elegans fat-1 gene encoding an n-3 desaturase that converts n-6 to n-3 fatty acids in mammalian cells. The objective of this study was to examine the effect of alteration in n-6/n-3 fatty acid ratio on the invasive potential of human lung cancer A549 cells. Adenovirus-mediated gene transfer of the n-3 desaturase resulted in a marked reduction of n-6/n-3 fatty acid ratio, especially the ratio of arachidonic acid (AA) to eicosapentaenic acid (EPA). Cell adhesion assay showed that cells expressing fat-1 gene had a delayed adhesion and retarded colonization. Matrigel assay for invasion potential indicated a 2-fold reduction of cell migration in the fat-1 transgenic cells when compared with the control cells. An increased apoptosis was also observed in the fat-1 transgenic cells. Microarray and quantitative PCR revealed down-regulation of several adhesion/invasion related genes (MMP-1, integrin-{alpha}2 and nm23-H4) in the fat-1 transgenic cells. These results demonstrate that decreased n-6/n-3 fatty acid ratio reduces the invasion potential of human lung cancer cells by probably down-regulation of cell adhesion/invasion related molecules, suggesting a role for the ratio of n-6 to n-3 fatty acids in cancer prevention and treatment.


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Proc. Natl. Acad. Sci. USAHome page
S. Xia, Y. Lu, J. Wang, C. He, S. Hong, C. N. Serhan, and J. X. Kang
Melanoma growth is reduced in fat-1 transgenic mice: Impact of omega-6/omega-3 essential fatty acids
PNAS, August 15, 2006; 103(33): 12499 - 12504.
[Abstract] [Full Text] [PDF]



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