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目的:探讨ω-3多不饱和脂肪酸和三羟异黄酮孕期营养干预对子代大鼠乳腺癌增殖细胞核抗原(PCNA)、雌激素受体(ER)、乳腺癌易感基因1(BRCA1)表达的影响。方法:怀孕大鼠随机分为正常对照组、ω-3多不饱和脂肪酸组、三羟异黄酮低剂量组、三羟异黄酮高剂量组、ω-3多不饱和脂肪酸和三羟异黄酮混合组。选用其雌性子代进行甲基亚硝基脲(MNU)诱导乳腺癌。其中母体为正常对照的分别为子代的正常对照组(Con)和模型组(Mod),其余分组按照母体暴露情况进行划分,分别为ω-3多不饱和脂肪酸组(ω-3PUFA)、三羟异黄酮低剂量组(LGEN)、三羟异黄酮高剂量组(HGEN)、ω-3多不饱和脂肪酸和三羟异黄酮混合组(ω-3PUFA+GEN)。观察其乳腺癌发生情况,同时采用RT-PCR和免疫组化检测正常乳腺组织和乳腺癌组织中PCNA、ER和BR-CA1的mRNA或蛋白表达水平。结果:ω-3多不饱和脂肪酸和三羟异黄酮孕期营养干预后可以减少雌性子代MNU诱导乳腺癌的发生,与Con组比较,Mod组乳腺癌组织中BRCA1和ER mRNA表达水平上调,PCNA、ER表达量增加。与Mod组比较,ω-3PUFA组、GEN组乳腺癌组织中BRCA1、ER mRNA及PCNA、ER表达量明显降低。结论:孕期暴露于ω-3PUFA和GEN可降低雌性子代MNU诱导乳腺癌的发生,并下调PCNA、ER和BRCA1的表达量。
Objective: To investigate the effects of nutritional interventions of ω-3 polyunsaturated fatty acids and genistein on the expression of proliferating cell nuclear antigen (PCNA), estrogen receptor (ER), and breast cancer susceptibility gene 1 (BRCA1) Impact. Methods: Pregnant rats were randomly divided into normal control group, ω-3 polyunsaturated fatty acid group, genistein low dose group, genistein high dose group, ω-3 polyunsaturated fatty acid and genistein mixed group. Female progeny were selected for methylnitrosourea (MNU) -induced breast cancer. Among them, the normal controls were the normal control group (Con) and the model group (Mod), and the other groups were divided according to the maternal exposure, which were ω-3 polyunsaturated fatty acid group (ω-3 PUFA) Genistein low dose group (LGEN), genistein high dose group (HGEN), ω-3 polyunsaturated fatty acid and genistein mixed group (ω-3 PUFA + GEN). Meanwhile, the mRNA and protein expression of PCNA, ER and BR-CA1 in normal breast tissues and breast cancer tissues were detected by RT-PCR and immunohistochemistry. Results: The nutritional intervention of ω-3 polyunsaturated fatty acids and genistein during pregnancy could reduce the incidence of breast cancer in MNU-induced female offspring. Compared with Con group, the expression of BRCA1 and ER mRNA in breast cancer tissues was increased , ER expression increased. Compared with Mod group, the expression of BRCA1, ER mRNA and PCNA, ER in omega-3 PUFA group and GEN group were significantly decreased. CONCLUSION: Exposure to omega-3 PUFAs and GEN during pregnancy reduces the incidence of breast cancer in MNU-induced female offspring and down-regulates the expression of PCNA, ER and BRCA1.