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KMID : 0613820180280080945
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Journal of Life Science
2018 Volume.28 No. 8 p.945 ~ p.954
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Effect of ω3-Fatty Acid Desaturase Gene Expression on Invasion and Tumorigenicity in Human Tongue Squamous Cell Carcinoma Cells
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Hong Tae-Hwa
Shin So-Yeon
Han Seung-Hyeon
Hwang Byung-Doo
Im Kyu
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Abstract
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Omega-3 polyunsaturated fatty acids (ω3-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ω3-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ω3 fatty acids, a stable SCC-9 cell line expressing the ω3-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ω3 fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.
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KEYWORD
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DHA, invasion, MMP, SCC, ω3-desaturase
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