Inhibitory effect of resveratrol on MNNG-induced endometrial carcinogenesis based on estrogen metabolism regulation / 中国药理学通报

ABSTRACT

Aim To observe the changes of estrogens and their metabolites in endometrial cancer mice, and preliminarily explore its potential mechanism of action from the perspective of estrogen homeostasis regulation. Methods EC mouse model was induced by MNNGT. The mice were randomly divided into control group, Res group, MNNG group and MNNG + Res group. HE staining was used to determine tumorigene-sis. qPCR was used to detect the mRNA expression levels of Ccndl, CK-19 , Erbb2. E1, E2, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 16α-OHE2 2-OHE!, 4-OHEj, 2-OHE1 and 4-OHE1 in serum and litems of mice were detected by LC-MS/MS. Results The number of endometrial glands in MNNG group sig-nificantly increased, while the sulcus could be observed in the foci. MNNG + Res group had mild edema of the myometrium, and the endometrium tended to assume its normal state. The mRNA expressions of Cc-ndl and Erbb2 of MNNG group were significantly high-er than those in control group, significantly decreased after combined administration of Res. In MNNG group, the levels of 2-MeOE2, 2-MeOE, and 4-MeOE, in serum and uterine tissue samples significantly decreased, while the content of 4-OHE2 significantly increased . While after treatment with Res, the content of 2-MeOE2 and 2-MeOE1 in uterine tissue significantly increased, 4-MeOE, in serum tissue also increased significantly, while 4-0HE2 content markedly decreased in serum and uterine tissues. Conclusions For the imbalance of estrogen homeostasis in EC mice, res-veratrol can up-regulate the content of estrogen metabolite 2-MeOE2 , reduce the content of 4-OHE2, and in-hibit the development of EC.