不同膳食脂肪酸对大鼠乳腺癌组织脂肪酸组成和脂代谢基因表达的影响

目的探讨不同膳食脂肪酸组成影响大鼠乳腺癌发生、发展的可能分子机制。方法用8种不同膳食脂肪酸组成(SFA、MUFA、n-6PUFA、n-3PUFA、1∶1n-6/n-3、5∶1n-6/n-3、10∶1n-6/n-3、1∶2∶1S/M/P其中n-6/n-31∶1)喂养SD雌性大鼠,并在大鼠乳腺癌模型的基础上,用气相色谱内标法观察大鼠乳腺组织脂肪酸组成改变,RT-PCR分析组织脂代谢调控基因(FAS、COX-2和5-LOX)的表达。结果在不同膳食脂肪酸构成中,只有1∶1n-6/n-3能有效抑制大鼠乳腺癌的发生。不同膳食脂肪酸构成可导致大鼠乳腺组织脂肪酸组成发生相应变化,且各组间的脂肪酸含量有显著差异。高乳腺癌诱发的SFA、MUFA、n-6PUFA、5∶1n-6/n-3、10∶1n-6/n-3和1∶2∶1S/M/P喂养组乳腺组织含有较多的C18∶1、C18∶2和C20∶4,而EPA和DHA含量极少。无或低乳腺癌诱发的n-3PUFA和1∶1n-6/n-3喂养组乳腺组织EPA和DHA明显增多,C20∶4含量显著减少。RT-PCR结果显示1∶1n-6/n-3低诱癌组较相应对喂组上调FAS、COX-2和5-LOXmRNA表达力度明显弱于其它高乳腺癌诱发组。结论不同膳食脂肪酸组成能明显改变大鼠乳腺组织脂肪酸组成,进而影响脂代谢基因FAS、COX-2和5-LOX表达,可能是大鼠乳腺癌发生的分子机制之一。

EFFECT OF DIFFERENT DIETARY FATTY ACIDS ON FATTY ACID COMPOSITIONS AND LIPID METABOLIC GENE EXPRESSION IN BREAST CANCER TISSUES OF RATS

Objective: To study the underlying mechanism of different dietary fatty acids composition on occurrence and progression of breast cancer. Method: Female SD 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). After the model of breast cancer was established, the fatty acid compositions in the mammary adipose tissue were analyzed by gas chromatography. The expression of lipid metabolic genes (FAS, COX-2 and 5-LOX) were assayed by RT-PCR. Results: Among the different dietary fatty acid compositions, 1∶1 n-6/n-3 had inhibitory effect on the breast cancer development. The fatty acid composition of mammary adipose tissue were markedly altered by these fatty acids intake, and their differences in various groups were statistically significant. The high levels of C18∶1, C18∶2 andC20∶4 along with the low levels of EPA and DHA were found in mammary adipose tissues of cancer growth-enhancing groups (SFA, MUFA, n-6 PUFA, 5∶1 n-6/n-3, 10∶1 n-6/n-3 and 1∶2∶1 S/M/P). whereas increased concentration in EPA and DHA along with decreased concentration in C20∶4 were discovered in mammary adipose tissues in n-3 PUFA and 1∶1 n-6/n-3 groups. Moreover, compared with the pair-fed groups, the expressions of FAS, COX-2 and 5-LOX mRNA were significantly up-regulated in mammary adipose tissues of the breast cancer groups except n-3 PUFA group, and the up-regulation was lowest in 1∶1 n-6/n-3 group. Conclusion: Different dietary fatty acids could obviously change the fatty acid compositions of mammary adipose tissue in which the expression of lipid metobolic genes may play key role in regulating the inducement of breast cancer in rats.