Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells.
Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells.
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发表时间：
2002-03
影响因子：
2
通讯作者：
Y. Ge;Zhihong Chen;Z. B. Kang;J. Cluette-Brown;M. Laposata;J. Kang
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作者：
Y. Ge;Zhihong Chen;Z. B. Kang;J. Cluette-Brown;M. Laposata;J. Kang
背景：目前来自实验和人体研究的证据表明，omega-6多不饱和脂肪酸(n-6 PUFAs)促进乳腺肿瘤的发展，而长链n-3多不饱和脂肪酸(n-3 PUFAs)则具有抑制作用。N-6和n-3脂肪酸的比例似乎是控制肿瘤发展的一个重要因素。人体细胞通常有非常高的n-6/n-3脂肪酸比率，因为它们不能将n-6多不饱和脂肪酸转化为n-3多不饱和脂肪酸，因为线虫中缺乏n-3去饱和酶。材料与方法用腺病毒策略将编码n-3脂肪酸去饱和酶的线虫Fat-1基因导入人乳腺癌细胞，检测细胞中n-6/n-3脂肪酸比例及细胞生长情况。结果携带FAT-1基因的重组腺病毒感染MCF-7细胞后，其n-3脂肪酸去饱和酶基因高表达。脂质分析显示，n-3多不饱和脂肪酸含量显著增加，n-6多不饱和脂肪酸含量大幅下降，n-6/n-3比值由12.0变为0.8。因此，在表达FAT-1基因的细胞中，来自n-6多不饱和脂肪酸的二十烷基类化合物的产生显著减少。重要的是，基因转移诱导了大量细胞死亡，抑制了细胞增殖。结论n-3脂肪酸脱氢酶基因转移作为一种新的方法，可以有效地改变人肿瘤细胞的n-6/n-3脂肪酸比例，具有抗肿瘤作用，而不需要外源性n-3多不饱和脂肪酸的补充。这些数据还增加了对n-3脂肪酸和n-6/n-3比率在癌症预防和治疗中的作用的了解。
BACKGROUND Current evidence from both experimental and human studies indicates that omega-6 polyunsaturated fatty acids (n-6 PUFAs) promote breast tumor development, whereas long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) exert suppressive effects. The ratio of n-6 to n-3 fatty acids appears to be an important factor in controlling tumor development. Human cells usually have a very high n-6/n-3 fatty acid ratio because they cannot convert n-6 PUFAs to n-3 PUFAs due to lack of an n-3 desaturase found in C. elegans. MATERIALS AND METHODS Adenoviral strategies were used to introduce the C. elegans fat-1 gene encoding an n-3 fatty acid desaturase into human breast cancer cells followed by examination of the n-6/n-3 fatty acid ratio and growth of the cells. RESULTS Infection of MCF-7 cells with an adenovirus carrying the fat-1 gene resulted in a high expression of the n-3 fatty acid desaturase. Lipid analysis indicated a remarkable increase in the levels of n-3 PUFAs accompanied with a large decrease in the contents of n-6 PUFAs, leading to a change of the n-6/n-3 ratio from 12.0 to 0.8. Accordingly, production of the eicosanoids derived from n-6 PUFA was reduced significantly in cells expressing the fat-1 gene. Importantly, the gene transfer induced mass cell death and inhibited cell proliferation. CONCLUSION The gene transfer of the n-3 fatty acid desaturase, as a novel approach, can effectively modify the n-6/n-3 fatty acid ratio of human tumor cells and provide an anticancer effect, without the need of exogenous n-3 PUFA supplementation. These data also increase the understanding of the effects of n-3 fatty acids and the n-6/n-3 ratio on cancer prevention and treatment.