Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes.
Recent studies have shown opposing effects of n-6 and n-3 fatty acids on the development of cancer and suggest a role for the ratio of n-6 to n-3 fatty acids in the control of cancer. However, whether an 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 Caenorhabditis 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 the 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 the n-6/n-3 fatty acid ratio, particularly the ratio of arachidonic acid to eicosapentaenic acid. Cell adhesion assay showed that the 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 polymerase chain reaction revealed a downregulation of several adhesion/invasion-related genes (MMP-1, integrin-alpha2 and nm23-H4) in the fat-1 transgenic cells. These results demonstrate that a decreased n-6/n-3 fatty acid ratio reduces the invasion potential of human lung cancer cells by probably downregulating the cell adhesion/invasion-related molecules, suggesting a role for the ratio of n-6 to n-3 fatty acids in the prevention and treatment of cancer.
Xia
Shu-Hua
SH
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Wang
Jingdong
J
Kang
Jing X
JX
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics*; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000502:physiology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D061107:Nucleoside Diphosphate Kinase D; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D039421:Integrin alpha2; D007797:Laminin; D054778:NM23 Nucleoside Diphosphate Kinases; D011509:Proteoglycans; C059485:matrigel; D016718:Arachidonic Acid; D003094:Collagen; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases; C078565:omega-3 fatty acid desaturase; C517938:NME1 protein, human; C517946:NME4 protein, human; D061107:Nucleoside Diphosphate Kinase D; D009701:Nucleoside-Diphosphate Kinase; D020781:Matrix Metalloproteinase 1