Carcinogenesis Advance Access published online on January 20, 2005
Carcinogenesis, doi:10.1093/carcin/bgi019
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1 Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114
* To whom correspondence should be addressed. 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-
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
Jing X. Kang, E-mail: kang.jing{at}mgh.harvard.edu
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Abstract
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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