白藜芦醇对子宫内膜癌细胞模型雌激素内稳态的影响

Effect of resveratrol on estrogen homeostasis in mice model of early endometrial cancer

目的:观察子宫内膜癌细胞雌激素及其代谢产物的变化规律,考察白藜芦醇对子宫内膜癌雌激素内稳态的影响,并从雌激素内稳态的角度初步探究其潜在的作用机制.方法:本实验分为正常子宫内膜细胞对照组(Control组)和白藜芦醇给药组(Res组),子宫内膜癌细胞模型组(Model组)和模型组给予白藜芦醇治疗组(Model+Res组),RT-PCR检测各肿瘤标志物的mRNA表达;利用LC-MS/MS法检测子宫内膜细胞内外液中雌激素及其代谢产物的含量变化,并结合SIMCA 14.0软件对数据进行分析,寻找疾病差异标志物.结果:Model组Ccnd1和Erbb2 mRNA表达水平较Control组显著升高(P<0.05).经SIMCA 14.0软件分析可知,子宫内膜癌细胞内外液样本中2-甲基雌二醇(2-MeOE2),2-甲基雌酮(2-MeOE1),和4-甲基雌酮(4-MeOE1)的浓度水平显著下降(P<0.01),4-羟基雌二醇(4-OHE2)含量显著增加(P<0.05),在给予Res治疗后,子宫内膜癌细胞外液中4-MeOE1的含量显著升高(P<0.05),子宫内膜癌细胞内液中2-MeOE2和2-MeOE1含量显著升高(P<0.05),4-OHE2在子宫内膜癌细胞内外液中的含量均显著降低(P<0.05).结论:子宫内膜癌细胞内外液雌激素代谢产物2-MeOE2含量降低和4-OHE2含量升高,可能是诱导子宫内膜癌细胞雌激素出现代谢紊乱的原因之一,白藜芦醇能够逆转这两种代谢产物的相对失衡.

Objective:To observe the changes of estrogen and its metabolites in endometrial cancer cells, to investigate the effect of resveratrol on estrogen homeostasis in endometrial cancer, and to explore its potential from the perspective of estrogen homeostasis. The mechanism of action. Methods:The experiment was divided into normal endometrial cell control group (Control group) and resveratrol administration group (Res group), endometrial cancer cell model group (Model group) and model group given resveratrol treatment group (Model + Res group), RT-PCR was used to detect the mRNA expression of each tumor marker;LC-MS/MS method was used to detect the changes of estrogen and its metabolites in the endometrial cells, and combined with SIMCA 14.0 software. The data was analyzed to find markers of disease differences. Results:The mRNA levels of Ccnd1 and Erbb2 were significantly higher in the Model group than those in the Control group (P<0.05). According to SIMCA 14.0 software analysis, the concentration levels of 2-MeOE2, 2-MeOE1 and 4-MeOE1 in the internal and external fluid samples of endometrial cancer cells decreased significantly (P<0.01), and the content of 4-OHE2 increased significantly (P<0.05). After treatment with Res, the content of 4-MeOE1 in the extracellular fluid of endometrial cancer cells was significantly increased (P<0.05), and the contents of 2-MeOE2 and 2-MeOE1 in the endometrial cancer cells were significantly increased (P<0.05), the content of 4-OHE2 in the inner and outer fluid of endometrial cancer cells was significantly decreased (P<0.05). Conclusion:The decrease of 2-MeOE2 and 4-OHE2 in the endometrial cancer cells may be one of the causes of the metabolic disorder of estrogen in endometrial cancer cells. Resveratrol can reverse this. The relative imbalance between the two metabolites.