Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA.
Br J Cancer. 2011 Nov 22;105(11):1750-8. doi: 10.1038/bjc.2011.434. Epub 2011 Oct 20.
The intake of dietary fatty acids is highly correlated with the risk of various cancers. Linoleic acid (LA) is the most abundant polyunsaturated fat in the western diet, but the mechanism(s) by fatty acids such as LA modulate cancer cells is unclear. In this study, we examined the role of LA in various steps in gastric cancer progression.
The difference in gene expression between LA-treated and untreated OCUM-2MD3 gastric carcinoma cells was examined by mRNA differential display. The involvement of candidate genes was examined by oligo- and plasmid-mediated RNA interference. Biological functions of several of these genes were examined using in vitro assays for invasion, angiogenesis, apoptosis, cell viability, and matrix digestion. Angiogenesis in vivo was measured by CD-31 immunohistochemistry and microvessel density scoring.
LA enhanced the plasminogen activator inhibitor 1 (PAI-1) mRNA and protein expression, which are controlled by PAI-1 mRNA-binding protein. LA-stimulated invasion depended on PAI-1. LA also enhanced angiogenesis by suppression of angiostatin, also through PAI-1. LA did not alter cell growth in culture, but increased dietary LA-enhanced tumour growth in an animal model.
Our findings suggest that dietary LA impacts multiple steps in cancer invasion and angiogenesis, and that reducing LA in the diet may help slow cancer progression.
饮食中脂肪酸的摄入与各种癌症的风险高度相关。亚油酸（LA）是西方饮食中最丰富的多不饱和脂肪，但脂肪酸（如 LA）调节癌细胞的机制尚不清楚。在这项研究中，我们研究了 LA 在胃癌进展的各个阶段中的作用。
通过 mRNA 差异显示检查 LA 处理和未处理的 OCUM-2MD3 胃癌细胞之间的基因表达差异。通过寡核苷酸和质粒介导的 RNA 干扰检查候选基因的参与。使用体外侵袭、血管生成、细胞凋亡、细胞活力和基质消化测定来检查其中一些基因的生物学功能。通过 CD-31 免疫组织化学和微血管密度评分测量体内血管生成。
LA 增强了纤溶酶原激活物抑制剂 1（PAI-1）mRNA 和蛋白表达，这受 PAI-1 mRNA 结合蛋白的控制。LA 刺激的侵袭依赖于 PAI-1。LA 还通过抑制血管抑素来增强血管生成，也通过 PAI-1。LA 不会改变培养中的细胞生长，但在动物模型中增加了饮食中的 LA 增强肿瘤生长。
我们的研究结果表明，饮食中的 LA 影响癌症侵袭和血管生成的多个步骤，减少饮食中的 LA 可能有助于减缓癌症进展。
