不同膳食脂肪酸对大鼠乳腺癌细胞核受体基因表达的影响

目的 探讨核受体基因表达在不同膳食脂肪酸影响大鼠乳腺癌发生中的作用。方法用8种不同膳食脂肪酸（饱和脂肪酸、单不饱和脂肪酸、n-6多不饱和脂肪酸、n-3多不饱和脂肪酸、1：1n-6／n-3多不饱和脂肪酸、5：1n-6／n-3多不饱和脂肪酸、10：1n-6／n-3多不饱和脂肪酸、1：2：1饱和脂肪酸／单不饱和脂肪酸／多不饱和脂肪酸其中n-6／n-3多不饱和脂肪酸1：1）喂养SD雌性幼年大鼠,采用50mg／kg的甲基亚硝基脲单次腹腔注射诱导大鼠乳腺癌发生,电镜观察大鼠乳腺细胞结构变化,BrdU体内标记法检测大鼠乳腺细胞增殖活性,RT—PCR分析乳腺组织过氧化物酶增殖活化受体（PPARβ和PPARγ）mRNA表达。结果 无乳腺癌诱发的各对照和n-3多不饱和脂肪酸诱癌组大鼠乳腺细胞超微结构正常,细胞增殖活性低。而有大鼠乳腺癌诱发的组织细胞内可见明显的腺癌标志,且高乳腺癌诱发的饱和脂肪酸、单不饱和脂肪酸、n-6多不饱和脂肪酸、5：1n-6／n-3多不饱和脂肪酸、10：1n-6／n-3多不饱和脂肪酸和1：2：1饱和脂肪酸／单不饱和脂肪酸／多不饱和脂肪酸喂养组大鼠乳腺细胞增殖活性升高（BrdU阳性率为21％～22％）,但1：1n-6／n-3多不饱和脂肪酸低诱癌组乳腺细胞增殖活性明显降低上述高乳腺癌诱发组（BrdU阳性率为13％,P〈0．05）。此外,过氧化物酶增殖活化受体作为与脂代谢密切相关的细胞核受体基因,1：1n-6／n-3多不饱和脂肪酸低诱癌组较相应对照组上调PPARβ和PPARγ mRNA表达力度明显弱于高乳腺癌诱发组。结论 不同膳食脂肪酸对PPAR基因表达的调节截然不同,这可能是差异性调节大鼠乳腺癌发生的分子机制之一。

Effects of different dietary fatty acid on expression of nuclear receptor genes in breast cancer of rats

OBJECTIVE: To study the effects of different dietary fatty acid on the expression of nuclear receptor genes in the breast cancer of rats. METHODS: Fifty-day-old female Sprangue-Dawley rats were fed on eight different diets containing following fatty acids: saturated fatty acid (SFA); monounsaturated fatty acid (MUFA); n-6 polyunsaturated fatty acid (PUFA); n-3 PUFA; 1:1 n-6/n-3; 5:1 n-6/n-3; 10:1 n-6/n-3; 1:2:1 S/M/P (n-6/n-3 at 1:1). The rats were given a single intraperitoneal injection of methyl-nitrosourea (MNU) at 50 mg/kg body weight to establish the rat model of mammary carcinogenesis, the ultrastructure changes of mammary gland cells in rats were observed by transmission electron microscope, the cell proliferation activity was detected by BrdU-labeled immunocytochemistry, and the expression of PPARbeta and PPARgamma mRNA were assayed by RT-PCR. RESULTS: There was no breast cancer occurring in control groups and the MNU-treated n-3 PUFA group, and the ultrastructure and proliferation activity of mammary gland cells in these groups were normal. In contrast, there appeared obvious marker of adenocarcinomas in mammary gland cells of MNU-induced breast cancer, and a high cell proliferation activity was found in tumor growth-enhancing groups (SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and S/M/P, 21% - 22% of BrdU-labeled cells), while a low cell proliferation activity was detected in rats fed with 1:1 n-6/n-3 diet (13% of BrdU-labeled cells, P < 0.05). Moreover, peroxisome proliferator-activated receptors (PPARs), as important nuclear receptor genes of relating lipid metabolism, the expressions of PPARbeta and PPARgamma mRNA were significantly up-regulated in mammary adipose tissues of MNU-induced breast cancer as compared with the control groups, but the expression levels of peroxisome proliferator-activated receptors (PPARs) in rats fed with 1:1 n-6/n-3 group were lowest (P < 0.05). CONCLUSION: The different dietary fatty acid compositions should diversely adjust the expression of PPARs gene in rats, which maybe have an important role in affecting incidence of breast cancer.